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Velvet Antler compounds targeting major cell signaling pathways in osteosarcoma - a new insight into mediating the process of invasion and metastasis in OS

  • Zhengyao Zhang , Pengfei Li , Tie Li , Changwei Zhao and Guoxiang Wang EMAIL logo
Published/Copyright: March 29, 2019
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Open Chemistry
From the journal Open Chemistry Volume 17 Issue 1

Abstract

Velvet antler is the only renewable bone tissue of mammalian animals, which consists of a variety of growth factors, amino acids and polypeptides. But the mechanism of high-speed proliferation without carcinogenesis is still mystifying. The previous study of this work found that the velvet antler peptides (VAP) could not only inhibit the proliferation and migration of osteosarcoma cell lines MG-63 and U2OS, but also induced U2OS apoptosis and inhibited MG-63 epithelial-mesenchymal transition (EMT) through TGF-β and Notch pathways. These results lead us to conclude that VAP has the potential ability to mediate osteosarcoma cells by regulating related signaling pathways and growth factors. Therefore, finding a new appropriate inhibitor for OS is a valuable research direction, which will give patients a better chance to receive proper therapy. From an applied perspective, this review summarized the effects of velvet antler, genes, growth factors and research progress of relative pathways and genes of osteosarcoma, which are poised to help link regenerative molecular biology and regenerative medicine in osteosarcoma pathogenesis.

Keywords: osteosarcoma; velvet antler; growth factors; pathways; EMT

1 Introduction

Osteosarcoma, derived from primitive bone-forming mesenchymal cells, is the most common primary bone malignancy that occurs most frequently in adolescents and elders over the age of 60 [1]. Osteosarcoma most frequently affects the growing ends of long bones and is often located adjacent to joints. Approximately one-half of all osteosarcomas affects the knee region, with the distal femur being the most commonly affected site [2]. Osteosarcoma is characterized by destruction of bone and soft tissue and is highly likely to be accompanied by metastasis of the cancer cells to the distal organ, where metastasis to the lung accounts for approximately 80%, with a poor prognosis. If clinical metastasis occurs, the patient’s five-year survival rate is between 20%-30% by the combination of conventional surgery and chemotherapy [3]. Deer velvet antler is one of the most important conventional Chinese medicines, the application of which was started two thousand years ago. It has been extensively used in traditional Chinese medicine (TCM) to treat a variety of diseases including degenerative disease (osteoarthritis), auto-immune or auto-inflammatory processes (rheumatoid arthritis and ankylosing spondylitis), infection (septic arthritis), idiopathic (juvenile idiopathic arthritis) and kidney diseases and so on. In a decade, researchers have extracted velvet antler peptides (VAP) by using ion exchange chromatography, gel filtration chromatography and high-performance liquid chromatography. Hence, the velvet antler contains a lot of growth factors such as insulin-like growth factor (IGF), nerve growth factor (NGF), epidermal growth factor (EGF) and transforming growth factor (TGF), which have different influences on osteosarcoma cells [4,5]. In addition, the progression of osteosarcoma is regulated by signaling pathways such as TGF-β, which can mediate the pro-apoptosis effects by doxorubicin [6] , and the inhibition of the Notch pathway can suppresses

Table 1

Summary of the validated growth factors in preclinical experiments of osteosarcoma.

Growth factorsTargetFunctions in cancer
Sirtuin 6[17]MMP9 ERK1/2Migration and invasion
Fractalkine[18]CX3CR1Osteosarcoma metastasis
EZH2[19]TUG1tumorigenesis
NKD2[20]unclearTumor growth and metastasis
HIF1α[21]COX2Carcinogenesis
VEGFMetastasis
Endocannabinoid/Endovanilloid [22]CB1/2Anti-proliferative, pro-apoptotic
Anti-invasive
CCL5/CCR5[23]VEGFTumor angiogenesis
BMP-9[24]SmadCell apoptosis
Bcl-2Proliferation and metastasis
MALAT1[25]PI3K/AKTProliferation and metastasis

osteosarcoma growth [7]. Wnt-β-catenin and PI3K/Akt can influence osteosarcoma cell proliferation and growth [8], and NF-κB can be used as a target to induce osteosarcoma cells apoptosis [9], thus the molecule-targeted treatment of tumors should be widely considered. Pathway research provides the basis for study of osteosarcoma diagnosis and drug targets. At the same time, during the progress of osteosarcoma formation, many genes have mutated expression and modified abnormally, including oncogene (Sema4d, Sema6d, ZNF217 and ZNF592) [10], tumor suppressor gene (Period2, Bax and P53) [11,12] and tumor migration gene (RANKL, CXCR4, RB1, MDM2) [13]. Identified and screened mutated genes and abnormally expressed genes are very important to treat and diagnose osteosarcoma. Chen et.al have found the extracts of velvet antler had a dose-response relationship for osteosarcoma cell-line UMR-106, when the concentration was higher than 0.972mg/L and lower than 97.2mg/L, samples inhibited the proliferation of the cells, when the concentration reached 97.2ml/L the role will change to promote, and the effects are increased with an increase in protein concentration [14]. However, its molecular mechanism is still unclear, which needs further study. Meanwhile, we have found that VAPs can inhibit the proliferation and migration of osteosarcoma cell lines MG-63 and U2OS. The VAP can also induce U2OS apoptosis and inhibit MG-63 epithelial-mesenchymal transition (EMT), while TGF-β and Notch pathways regulate these interactions. Thus, how far have we moved forward and what therapeutic strategy should we prefer for anti-pathway therapy? This review provides an overview of the most updated pathways and genes related in OS and discusses some clinical options in order to maintain or even improve progression-free survival.

2 Diagnosis and possible target therapies for osteosarcoma

In the recent years, the diagnosis and therapies of osteosarcoma have been improved a lot by the efforts of researchers. The conventional methods of diagnosis include performing biopsy of pathology tissue, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) and so on. The new method which used to diagnose osteosarcoma aims at detecting biomarkers including microRNAs, long non-coding RNAs, circulating tumor cells, and circulating tumor DNA. There are a lot of advantages in the new method, called liquid biopsy, when compared to conventional methods, such as, low sample volume, greater accuracy, less expensive, and easy detection [1,15].

Several pieces of evidence strongly support the potential capability of new therapies such as cellular therapy and gene therapy to eradicate osteosarcoma. Thus, clinical human trials using peptides, cytokines and dendritic cells have been performed [16]. Investigators have found a variety of growth factors and microRNAs which have effective impact on osteosarcoma. These findings can be innovative therapies for osteosarcoma to improve survival and prognosis.

3 Gene mutated in Cancer Bone Disease

There are numerous gene mutations and changes in expression in the process of osteosarcoma compared with normal people. It plays a pivotal role to identify and screen mutated genes for diagnosing and treating osteosarcoma. It is widely believed that cell carcinogenesis and tumor metastasis are caused by changes in genetic information. It has been found that some mutations and aberrant expressions can occur during osteosarcoma formation including oncogenes (e.g.,HER2, c-myc, c-fos), tumor suppressor genes (e.g., TP53, Rb, and p16) and tumor migration genes (CD44, MMP-9, and nm23) [36,37]. In recent years, some researchers tend to screen the changes of massive genes in osteosarcoma to optimize its diagnosis and treatment. Wang’s group screened for mutations in 339 cancer-related genes from 10 osteosarcoma patients through high-throughput sequencing and observed novel 85 mutinied genes in at least one patient, 39 mutinied genes in at least five patients (Table 2) [38]. In addition, 12 osteosarcoma metastasis genes have been identified from 31 patients by cDNA subtraction experiment (Table 3) [39]. Also, more genes were found by other studies which are related to osteosarcoma. MET one of the oncogenes, was causally involved in the pathogenesis of osteosarcoma. Overexpression of MET could promote the conversion of primary human osteoblasts into osteosarcoma cells, displaying phenotype of tumor in vitro and the distinguishing features of human osteosarcomas in vivo [40]. ErbB2 is another important gene in osteosarcoma. It has been demonstrated that high levels of ErbB2 in osteosarcoma cells could increase event-free survival and overall survival significantly. Moreover, a decreased level of ErbB2 was associated with poor prognosis of osteosarcoma patients. Thus, ErbB2 might serve as a potential therapeutic biomarker target for predicting the chemotherapy progress as an illustrative example [41]. COX2 also known as PTGS encodes the inducible isozyme. It is required for tumoursphere formation, but tumourspheres increase invasiveness and tumourigenicity in osteosarcoma. Therefore, it could be a potential target to treat osteosarcoma. Furthermore, the expression of COX2 elevated 141-fold in a cancer stem cells (CSC) pool and plays a vital role in various aspects of carcinogenesis including the promotion of angiogenesis and the down-regulation of apoptosis [42]. Therefore, COX-2 could be a biomarker in human osteosarcoma and the inhibition might be a possible way to improve therapeutic outcome [43]. CUL4B gene is located on the X chromosome and largely expressed in the nucleus. It can promote proliferation and invasion and inhibit apoptosis of human osteosarcoma. In addition, CUL4B can not only influence H2AK119 monoubiquitination but also H3K9 tri-methylation and DNA methylation, thus suppressing the expression of relevant genes including the tumor-suppressor IGFBP3 [44]. Since the gene mutation is a major cause in tumor occurrence and invasion, the possible applications of which can be used as identification of new biomarkers for more accurate and efficient diagnosis.

Table 2

Summary of the validated microRNA in preclinical experiments of osteosarcoma.

microRNATargetFunctions in cancer
miR-137[26]FXYD6Cell growth
miR-154[27]Wnt5aTumor suppressor
miR-646[28]FGF2Osteosarcoma cells metastasis
miR-23a[29]PTENCell migration and invasion
miR-153[30]TGF-β2Cell proliferation and invasion
miR-221[31]PI3KOsteosarcoma cells survival Cisplatin resistance
miR-29b[32]CDK6Osteosarcoma cells proliferation Cells metastasis
miR-150[33]ROCK1Osteosarcoma cells proliferation Invasion and migration
miR-543[34]PRMT9 HIF-1αOsteosarcoma cells proliferation and glycolysis
miR-16[35]IGF1RCell proliferation
Table 3

Changes in the expression of mutated genes in bone cancer [45].

GeneFunctionGeneFunction
ALKoncogeneGLTSCR1tumor suppressor gene
ASPMcell divisionHSP90AA1encodes heat shock protein90AA1
ATRXtranscriptional regulation and chromatin remodelingITGB3participate in cell adhesion and cell-surface mediated signaling
BCRactivate GTPaseKDRmediate endothelial proliferation, survival, migration
BL0C1S2unknownLATS2tumor suppressor gene
BRCA1tumor suppressor geneMLH3DNA mismatch repair genes
BRCA2tumor suppressor geneMMP14breakdown extracellular matrix
BRIP1a target of germline cancer-inducing mutationsRCBTB1induced cellular hypertrophy in vascular smooth muscle cells
CCNA2regulate cell cycleRECQL4Maintain DNA stability of telomere and mitochondrial
CDKN2Atumor suppressor geneRNASELmediate tumor cell apoptosis
CHATcatalyze the biosynthesis of the acetylcholineRNU6-28PPseudogene and is affiliated with the snRNA class
CYP2D6drug metabolismRPS6KB1promote protein synthesis, cell growth, and cell proliferation
DLC1tumor suppressor geneSRCproto-oncogene
DMBT1tumor suppressor geneTMPRSS11Aregulate cell growth and cell cycle arrest
DPYDpyrimidine catabolismTNCinfluence migration of neurons and axons, synaptic plasticity and neuronal regeneration
EGFRinduce receptor dimerization, tyrosine autophosphorylation and cell proliferation.TP53tumor suppressor gene
EML4participate in microtubule formationTRIM3participate in myosin V-mediated cargo transport
FANCAparticipate in inter-strand DNA cross-link repair and maintain normal chromosome stabilityXPADNA repair
FN1cell adhesion and migrationXPCDNA repair
GATA3regulate cell proliferation

4 Pathways in a Physiological and Pathological Context in the Osteosarcoma

4.1 TGF-β pathways

Latest research found that osteosarcoma can deregulate bone remolding and break the balance between bone formation and bone resorption. After deregulating bone remolding, it is induced to release TGF-β in bone matrix [47]. Antler polypeptides contain a variety of growth factors including TGF-β, they can become the source of exogenous TGF-β which can inhibit proliferation of osteosarcoma and slow down the disease and make the prognosis of patients better. It has been confirmed that high concentration of exogenous TGF-β can inhibit the proliferation of osteosarcoma MG-63 cells, however, the

Table 4

Gene name, functions of 12 reference metastasis genes involved in Osteosarcoma [46].

GeneFunctionsGeneFunctions
SMADsignal transducers and transcriptional modulatorsNSE2mediate the attachment of a SUMO protein to proteins, nuclear transport, transcription, chromosome segregation and DNA repair.
RANKLregulate osteoclast differentiation, T cell-dependent immune response and cell apoptosisRUNX2regulate osteoblastic differentiation, skeletal gene expression and skeletal morphogenesis and act as a scaffold for nucleic acids
Ezrinparticipate in cell surface structure adhesion, migration and organizationTGF-βregulate cell proliferation, differentiation and growth, and modulate expression and activation of other growth factors
IL-8mediate inflammatory response and induces chemotaxis and phagocytosisMAPKregulate cell proliferation, differentiation, signaling transcription and survival and apoptosis
β4 integrinmediate cell-matrix or cell-cell adhesion and regulate gene expressionSPP1participate in biomineralization, bone remodeling and act as an anti-apoptotic factor
CLIC5participate in hair cell stereocilia formation, myoblast proliferationTP53tumor suppressor gene
Figure 1 Velvet antler polypeptides regulate TGF-β in osteosarcoma cells. Note: The VAP inhibit the expression of EMT transcriptional factors and E-cadherin by down-regulating the TGF-β pathway in MG-63 cells, which interfere the invasion and migration afterwards.
Figure 1

Velvet antler polypeptides regulate TGF-β in osteosarcoma cells. Note: The VAP inhibit the expression of EMT transcriptional factors and E-cadherin by down-regulating the TGF-β pathway in MG-63 cells, which interfere the invasion and migration afterwards.

lower concentration of TGF-β had no significant effect on it. Furthermore, exogenous TGF-β can inhibit the growth of MG- 63 cells cultured in vitro, which can increase the distribution of MG-63 cells in G1 phase and prevent the cells from entering S phase [48]. Exogenous TGF-β can make MG- 63 cells overexpressing a TGF-β inducible early gene (TIEG), and finally inhibit osteocalcin synthesis. While numerous studies have demonstrated that high expression of bone calcium in bone cells and osteosarcoma cells can inhibit the synthesis of osteocalcin then inhibit the proliferation of osteosarcoma cells [49]. Although researchers have confirmed the inhibitive role of TGF-β in tumorigenesis, it has on the contrary been shown to enhance metastasis of tumor cells and promote advanced tumors invasiveness [50]. TGF-β is a double-edged sword in cancer, on the one hand it can suppress tumor growth potently, on the other hand, it can also enhance invasion and metastasis of cancer by suppressing miR-143, inducing epithelial-mesenchymal transition (EMT) [51,52], which plays a vital role in tumor invasion and metastasis [53]. Furthermore, it has been reported that TGF-β can induce the expression of Snail which could repress the expression of E-cadherin, an important tumor suppressor [54]. Though TGF-β is involved in the EMT process, VAP has been shown to block the binding of TGF-β1 with its receptors, TGF-β receptor1 and 2, and inhibit the downstream activated pathway [55] (Figure1). It has also been confirmed that TGF-β1 not only stimulates the growth of osteosarcoma but also reduces the proliferative potential ability of osteosarcoma by inducing the expression of IGFBP-3 [56]. In addition to osteosarcoma, the antler polypeptide also affects other tumors. Tang et al. demonstrated that the top VAP can inhibit the migration of prostate cancer cells by downregulating the expression of its relevant gene, such as MMP-9 and VEGF [57].

4.2 Notch signaling pathways

The Notch signaling pathway includes Notch1, Notch2, Jag1, DLL1, DLL4, Hey1/Hey2 and CSL. It is implicated as a key mediator in a number of various cancers [58]. It is more like a double-edged sword, which can be used as an oncogene in one hand , while inhibiting tumor growth in some cases on the other hand [59]. In addition, regulating hes1 and DTX1 in notch signaling pathways can affect migration and invasion of osteosarcoma cells [60]. It has been confirmed that the expression of Notch and its target gene are up-regulated in osteosarcoma. Inhibiting Notch signaling by chemical and genetic ways can reduce nude mices’ tumor burden in vivo and decrease the proliferation of osteosarcoma cells in vitro [61]. Furthermore, it has been found that Notch pathways can regulate the osteosarcoma cell cycle by influencing the expression of cyclin E1, cyclin E2, c-Myc and so on. Notch signaling pathways play a very important role in osteosarcoma cell progression [62]. Besides these roles we have referred to, it also participates in EMT. The EMT progression can be arrested by the inhibition of notch signaling pathways [63]. Furthermore, notch pathways will become a mediator when some growth factors and drugs mitigate osteosarcoma. It has been found that BMP-9 can promote the growth of osteosarcoma, which is mediated by the notch signaling pathway. The study also demonstrated BMP-9 has effects on the receptors and ligands of notch signaling pathways including hey1, notch1, DLL1, JAG1 and JAG2 at the same time [64]. Moreover, some anticancer drugs exert anticancer effects by regulating notch signaling pathways. It has been shown that the anticancer drug, doxorubicin, can inhibit the proliferation of osteosarcoma cells by upregulating notch signaling pathways [65]. In addition, cinobufagin and curcumin can inhibit osteosarcoma growth in vivo, induce osteosarcoma cell apoptosis, cell growth inhibition, decrease cell survival, and improve mice survival by downregulating notch1 and its target gene [66,67]. Continuous medication can cause drug resistance in tumor cells, and the notch plays an important regulatory role in this process[68], which provides us a new way to cure osteosarcoma. In addition to growth factors and drugs, notch signaling pathways also participate in the process where microRNAs affect osteosarcoma. MicroRNA is a small non-coding RNA molecule found in plants, animals and some viruses, that functions in RNA silencing and post-transcriptional regulation of gene expression [69]. It is generally accepted that tumor recurrence often appears during the treatment of the tumor and the cancer stem cells play a key role in it. In recent years, researchers have found miR-135b can effect tumor metastasis and CSC-induced recurrence in osteosarcoma by regulating notch and Wnt/β-catenin signaling pathways, so they can be targeted to inhibit tumor metastasis and recurrence in osteosarcoma [70]. miR-34a-5p, miR-26a and miR-199b-5p also play an important role in osteosarcoma. The reduction of miR-26a can cause osteosarcoma metastasis and poor survival of osteosarcoma patients, miR26-a can also regulate cancer stem cells of osteosarcoma. But miR-26a only target Jagged1 which is a ligand in notch signaling pathways [71]. Moreover miR-34a-5p can promote multi-chemoresistance of osteosarcoma by down regulating DLL1 gene a ligand of notch signaling pathways and the inhibition of miRNA-199b-5p can change expression of notch pathway components [72,73]. These findings reveal that notch signaling pathways, and some microRNA can be novel targets for treating osteosarcoma and therapeutic options for osteosarcoma.

4.3 Wnt-β-catenin pathways

The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals into a cell through cell surface receptors. There are some proteins in them such as frizzled, disheveled, β-catenin, GSK3β, and axin scaffolding protein. They play a key role in cell cycle, apoptosis and tumorigenesis, and EMT [74]. It has been confirmed that it can decrease tumorigenicity, metastasis and EMT of osteosarcoma by downregulating LRP-5 which is a receptor of wnt in vivo and in nude mice experiments [75]. Thus LRP-5 can be a new target for inhibiting EMT. At the same time the activation of Wnt pathways can promote the tumorigenic phenotypes, and some receptors, ligands also up-regulated in osteosarcoma, therefore the treatment of osteosarcoma should aim at blocking Wnt pathways [76]. Rubin et al. provided Wnt Inhibitory Factor 1 can (WIF1) decreases tumorigenesis and metastasis in osteosarcoma cells line 143B cells and overexpression of WIF1 can inhibit lung metastasis in vivo in an orthotopic mouse model of osteosarcoma. Therefore, WIF1 is a potential target for treating osteosarcoma [77]. IWR-1, a tankyrase inhibitor which is a wnt/β-catenin signaling pathways inhibitor and a specifically cytotoxic for osteosarcoma cancer stem calls. It has been confirmed that IWR-1 not only can inhibit the growth of cancer stem cells in osteosarcoma in vivo and in vitro by targeting wnt signaling pathways but also can eradicate the aggressive osteosarcoma cancer stem cells and improve therapeutic outcomes [78] . DKK-3 is a Secreted Wnt Antagonist and involved in embryonic development through its interactions with the Wnt signaling pathway. Hoang et al. have confirmed that DDK-3 can decrease tumor growth and metastatic pulmonary nodules in nude mice. In addition, it can inhibit tumorigenic potential of osteosarcoma, decrease osteosarcoma cell motility in cells. So, we can make DDK3 as target to treat osteosarcoma [79]. Zhang et al. revealed that parathyroid hormone type 1 receptor (PTHR1) can promote malignancy for osteosarcoma through activation of wnt and angiogenesis signaling pathways. They have analyzed the microarray data extracted from the Gene Expression Omnibus (GEO) database and compared with PTHR1 knockdown samples [80]. However, a different opinion has been put forward that wnt signaling may act as a tumor repressor in osteosarcoma which is in contrast with its oncogenic role in other tumors [81]. Some medicines also exert their role by targeting wnt/β-catenin signaling pathways. Triptolide(TPL) is a diterpenoid epoxide which is produced by the thunder god vine. It can inhibit angiogenesis and induce cell apoptosis in osteosarcoma cells in a dose dependent manner through down-regulating Wnt/β-Catenin signaling [82]. Together, these findings have revealed that wnt/βcatenin could be a key pathway for treating osteosarcoma.

4.4 NF-κB pathway

NF-κB is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB plays a pivotal role in cell growth, apoptosis, migration and invasion of osteosarcoma [83]. Aspirin is a medication used to treat pain, fever, or inflammation. However, it has been confirmed that aspirin can influence osteosarcoma procession too. Kang et al. have demonstrated that aspirin can reduce cell viability and the more doses and time the better effects in osteosarcoma cells. Moreover, aspirin can also repress the migration and invasion of osteosarcoma cells and decrease osteosarcoma metastases to the lungs in nude mouse through regulating NF-κB pathway [84]. Thymoquinone is a phytochemical compound found in the plant Nigella sativa. It can inhibit cell growth and effectively induce tumor cell apoptosis and exert antiproliferative effects on several cancer cells in vitro. In addition, thymoquinone can inhibit tumor angiogenesis and tumor growth by downregulating NF-κB and its regulated molecules. Not only can thymoquinone inhibit osteosarcoma growth but also it can enhance sensitivity to chemotherapeutic agents [85]. Furthermore, NF-κB can contact with wnt pathway, wnt10b is a member of the wnt family which could upregulate interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α), known inducers of NF-κB [86].

4.5 PI3K/Akt Pathway

PI3K-Akt pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K (phosphatidylinositol 3-kinase) and Akt (Protein Kinase B). It is well known to be a major cell survival pathway and it can enhance resistance to apoptosis if activated [87]. Apo2L/TRAIL is a member of the tumor necrosis factor (TNF) family, which can induce apoptosis of cancer cells. It can induce osteosarcoma cell U2OS apoptosis by inhibiting akt expression and then reduce expression of Bcl-2 and activate caspase-9. Furthermore, it can also decrease osteosarcoma cell drug resistance by regulating Akt pathway [88,89]. Geraniin is an activated compound isolated from Geranium sibiricum. It has been found that Geraniin suppresses matrix metalloproteinase-9 (MMP-9) expression in a dose dependent manner and then inhibits the migration and invasion of osteosarcoma cells by suppressing the phosphorylation of the extracellular signal regulating kinase (ERK)1/2, phosphatidylinositide-3-kinase (PI3K), and Akt pathways [90]. miR-221 is an oncogenic microRNA and one of the most commonly upregulated miRNAs in cancer. It targets PTEN leading to activation of the Akt pathway, which is known as a major cell survival pathway in many cancers. It has been confirmed that knockdown of miR-221 in osteosarcoma cells can downregulate p-Akt expression, promote osteosarcoma cells apoptosis and lower cisplatin resistance through regulating PI3K/AKT pathway [91]. Some medicines can exert their roles through this pathway. Dryofragin is a phloroglucinol derivative extracted from Dryopteris fragrans. It has been found to be able to inhibit tumor proliferation and induce apoptosis. Moreover, in recent years it has been confirmed that dryofragin can suppress the migration and invasive ability of U2OS cells, downregulate the expression of MMP-2 and MMP-9 and upregulate the expression of TIMP-1 and TIMP-2 through PI3K/AKT and p38 MAPK signaling pathways [92]. Tricetin is a flavone, a type of flavonoid, that can also inhibit the metastasis of human osteosarcoma cells by transcriptionally repressing MMP-9 via p38 and Akt pathways [93]. All of them can be potentially used as anti-cancer agents for osteosarcoma treatment and supplement of osteosarcoma chemotherapy.

4.6 Other signaling pathways

Rheum palmatum L. is a common Chinese herb, also called Chinese rhubarb, ornamental rhubarb. Rheum palmatum L. has been used for anti-inflammatory and chronic liver diseases, and some cancer. In recent years, it has been indicated that Crude Extract of Rheum palmatum L. (CERP) can induce S phase arrest in osteosarcoma cells U2OS in a dose-dependent fashion, cause DNA damage and DNA condensation, up-regulate the expression of pro-apoptosis proteins such as Bax, Bak, p21, and p27 and activate caspase-3, -8, and -9 through mitochondrial-dependent pathways [94]. Aspidin PB is a phloroglucinol derivative isolated from Dryopteris fragrans (L.). Previous studies have found it can inhibit fibrogenesis [95] and induce apoptosis in human hepatocarcinoma HepG2 cells [96]. Moreover, it also has been confirmed that Aspidin PB can inhibit the proliferation of osteosarcoma cells in a dose-dependent and time-dependent manner and induce osteosarcoma cells apoptosis and cell cycle arrest through the p53/p21 and mitochondria-dependent pathways [97].

S-Adenosyl methionine (AdoMet) is a common co-substrate involved in methyl group transfers, transsulfuration, and aminopropylation. Naviglio’s group has confirmed that it can inhibit osteosarcoma cell proliferation by slowing-down cell cycle progression and by inducing apoptosis. Furthermore, it can downregulate ERK1/2 and STAT3 pathways to arrest cell cycle and induce osteosarcoma cell apoptosis [98]. Cucurbitacin B is class of tetracyclic triterpenoids and is extracted from Hemsleya endecaphylla (62 mg/72 g) and other plants [99]. It is the most abundant member of cucurbit family and has extensive pharmacological activities. For human osteosarcoma cells, it can downregulate MMP-2 and MMP-9 which contribute to the invasion and metastasis of tumor cells, upregulate the expression of pro-apoptotic proteins, and modulate JAK2/STAT3 signaling pathway [100].

5 Conclusion

Osteosarcoma is a complex, heterogenous, and interpatient, between different individuals and their living environment, disease. Therefore, successful treatment options are likely to arise from personalized precise treatment. There is paramount preclinical and clinical evidence for potent efficient activity of velvet antler and its extracts for use as therapeutics in bone fracture repair, osteoarthritis, osteoporosis and other bone diseases. Relating to TGF-β and Notch pathways, previous results suggested the involvement of VAP in regulation of proliferation and migration of osteosarcoma cells MG-63 as well as U2OS. Information about molecular mechanism and therapeutic targets of this reaction within the tumor cells needs to be elucidated. Furthermore, various growth factors such as sirtuin and NKD2 can regulate the osteosarcoma cell-cycle, and biomarkers will be essential to advance into clinical development to obtain meaningful and reliable answers on therapeutic ratios. Undoubtedly, further advances in our understanding of the pathology of osteosarcoma, and in the techniques for extracting the velvet antler, will strengthen our understanding of the ways in which the Chinese medicine counteracts cancer, and will aid in the development of anti-cancer therapeutic approaches.

  1. Conflicts of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no. 81503177 and 81573999) and Jilin science and technology development plan project (20160101158JC).

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Received: 2018-05-17
Accepted: 2018-09-06
Published Online: 2019-03-29

© 2019 Zhengyao Zhang et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 Public License.

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  43. Synthesis, characterization (IR, 1H, 13C & 31P NMR), fungicidal, herbicidal and molecular docking evaluation of steroid phosphorus compounds
  44. Analysis and Biological Evaluation of Arisaema Amuremse Maxim Essential Oil
  45. A preliminary assessment of potential ecological risk and soil contamination by heavy metals around a cement factory, western Saudi Arabia
  46. Anti- inflammatory effect of Prunus tomentosa Thunb total flavones in LPS-induced RAW264.7 cells
  47. Collaborative Influence of Elevated CO2 Concentration and High Temperature on Potato Biomass Accumulation and Characteristics
  48. Methods of extraction, physicochemical properties of alginates and their applications in biomedical field – a review
  49. Characteristics of liposomes derived from egg yolk
  50. Preparation of ternary ZnO/Ag/cellulose and its enhanced photocatalytic degradation property on phenol and benzene in VOCs
  51. Influence of Human Serum Albumin Glycation on the Binding Affinities for Natural Flavonoids
  52. Synthesis and antioxidant activity of 2-methylthio-pyrido[3,2-e][1,2,4] triazolo[1,5-a]pyrimidines
  53. Comparative study on the antioxidant activities of ten common flower teas from China
  54. Molecular Properties of Symmetrical Networks Using Topological Polynomials
  55. Synthesis of Co3O4 Nano Aggregates by Co-precipitation Method and its Catalytic and Fuel Additive Applications
  56. Phytochemical analysis, Antioxidant and Antiprotoscolices potential of ethanol extracts of selected plants species against Echinococcus granulosus: In-vitro study
  57. Silver nanoparticles enhanced fluorescence for sensitive determination of fluoroquinolones in water solutions
  58. Simultaneous Quantification of the New Psychoactive Substances 3-FMC, 3-FPM, 4-CEC, and 4-BMC in Human Blood using GC-MS
  59. Biodiesel Production by Lipids From Indonesian strain of Microalgae Chlorella vulgaris
  60. Miscibility studies of polystyrene/polyvinyl chloride blend in presence of organoclay
  61. Antibacterial Activities of Transition Metal complexes of Mesocyclic Amidine 1,4-diazacycloheptane (DACH)
  62. Novel 1,8-Naphthyridine Derivatives: Design, Synthesis and in vitro screening of their cytotoxic activity against MCF7 cell line
  63. Investigation of Stress Corrosion Cracking Behaviour of Mg-Al-Zn Alloys in Different pH Environments by SSRT Method
  64. Various Combinations of Flame Retardants for Poly (vinyl chloride)
  65. Phenolic compounds and biological activities of rye (Secale cereale L.) grains
  66. Oxidative degradation of gentamicin present in water by an electro-Fenton process and biodegradability improvement
  67. Optimizing Suitable Conditions for the Removal of Ammonium Nitrogen by a Microbe Isolated from Chicken Manure
  68. Anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Haloxylon salicornicum aqueous fraction
  69. The anti-corrosion behaviour of Satureja montana L. extract on iron in NaCl solution
  70. Interleukin-4, hemopexin, and lipoprotein-associated phospholipase A2 are significantly increased in patients with unstable carotid plaque
  71. A comparative study of the crystal structures of 2-(4-(2-(4-(3-chlorophenyl)pipera -zinyl)ethyl) benzyl)isoindoline-1,3-dione by synchrotron radiation X-ray powder diffraction and single-crystal X-ray diffraction
  72. Conceptual DFT as a Novel Chemoinformatics Tool for Studying the Chemical Reactivity Properties of the Amatoxin Family of Fungal Peptides
  73. Occurrence of Aflatoxin M1 in Milk-based Mithae samples from Pakistan
  74. Kinetics of Iron Removal From Ti-Extraction Blast Furnace Slag by Chlorination Calcination
  75. Increasing the activity of DNAzyme based on the telomeric sequence: 2’-OMe-RNA and LNA modifications
  76. Exploring the optoelectronic properties of a chromene-appended pyrimidone derivative for photovoltaic applications
  77. Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome
  78. Cyclodextrin potentiometric sensors based on selective recognition sites for procainamide: Comparative and theoretical study
  79. Greener synthesis of dimethyl carbonate from carbon dioxide and methanol using a tunable ionic liquid catalyst
  80. Nonisothermal Cold Crystallization Kinetics of Poly(lactic acid)/Bacterial Poly(hydroxyoctanoate) (PHO)/Talc
  81. Enhanced adsorption of sulfonamide antibiotics in water by modified biochar derived from bagasse
  82. Study on the Mechanism of Shugan Xiaozhi Fang on Cells with Non-alcoholic Fatty Liver Disease
  83. Comparative Effects of Salt and Alkali Stress on Antioxidant System in Cotton (Gossypium Hirsutum L.) Leaves
  84. Optimization of chromatographic systems for analysis of selected psychotropic drugs and their metabolites in serum and saliva by HPLC in order to monitor therapeutic drugs
  85. Electrocatalytic Properties of Ni-Doped BaFe12O19 for Oxygen Evolution in Alkaline Solution
  86. Study on the removal of high contents of ammonium from piggery wastewater by clinoptilolite and the corresponding mechanisms
  87. Phytochemistry and toxicological assessment of Bryonia dioica roots used in north-African alternative medicine
  88. The essential oil composition of selected Hemerocallis cultivars and their biological activity
  89. Mechanical Properties of Carbon Fiber Reinforced Nanocrystalline Nickel Composite Electroforming Deposit
  90. Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis
  91. Topical Issue on Applications of Mathematics in Chemistry
  92. Zagreb Connection Number Index of Nanotubes and Regular Hexagonal Lattice
  93. The Sanskruti index of trees and unicyclic graphs
  94. Valency-based molecular descriptors of Bakelite network BNmn
  95. Computing Topological Indices for Para-Line Graphs of Anthracene
  96. Zagreb Polynomials and redefined Zagreb indices of Dendrimers and Polyomino Chains
  97. Topological Descriptor of 2-Dimensional Silicon Carbons and Their Applications
  98. Topological invariants for the line graphs of some classes of graphs
  99. Words for maximal Subgroups of Fi24‘
  100. Generators of Maximal Subgroups of Harada-Norton and some Linear Groups
  101. Special Issue on POKOCHA 2018
  102. Influence of Production Parameters on the Content of Polyphenolic Compounds in Extruded Porridge Enriched with Chokeberry Fruit (Aronia melanocarpa (Michx.) Elliott)
  103. Effects of Supercritical Carbon Dioxide Extraction (SC-CO2) on the content of tiliroside in the extracts from Tilia L. flowers
  104. Impact of xanthan gum addition on phenolic acids composition and selected properties of new gluten-free maize-field bean pasta
  105. Impact of storage temperature and time on Moldavian dragonhead oil – spectroscopic and chemometric analysis
  106. The effect of selected substances on the stability of standard solutions in voltammetric analysis of ascorbic acid in fruit juices
  107. Determination of the content of Pb, Cd, Cu, Zn in dairy products from various regions of Poland
  108. Special Issue on IC3PE 2018 Conference
  109. The Photocatalytic Activity of Zns-TiO2 on a Carbon Fiber Prepared by Chemical Bath Deposition
  110. N-octyl chitosan derivatives as amphiphilic carrier agents for herbicide formulations
  111. Kinetics and Mechanistic Study of Hydrolysis of Adenosine Monophosphate Disodium Salt (AMPNa2) in Acidic and Alkaline Media
  112. Antimalarial Activity of Andrographis Paniculata Ness‘s N-hexane Extract and Its Major Compounds
  113. Special Issue on ABB2018 Conference
  114. Special Issue on ICCESEN 2017
  115. Theoretical Diagnostics of Second and Third-order Hyperpolarizabilities of Several Acid Derivatives
  116. Determination of Gamma Rays Efficiency Against Rhizoctonia solani in Potatoes
  117. Studies On Compatibilization Of Recycled Polyethylene/Thermoplastic Starch Blends By Using Different Compatibilizer
  118. Liquid−Liquid Extraction of Linalool from Methyl Eugenol with 1-Ethyl-3-methylimidazolium Hydrogen Sulfate [EMIM][HSO4] Ionic Liquid
  119. Synthesis of Graphene Oxide Through Ultrasonic Assisted Electrochemical Exfoliation
  120. Special Issue on ISCMP 2018
  121. Synthesis and antiproliferative evaluation of some 1,4-naphthoquinone derivatives against human cervical cancer cells
  122. The influence of the grafted aryl groups on the solvation properties of the graphyne and graphdiyne - a MD study
  123. Electrochemical modification of platinum and glassy carbon surfaces with pyridine layers and their use as complexing agents for copper (II) ions
  124. Effect of Electrospinning Process on Total Antioxidant Activity of Electrospun Nanofibers Containing Grape Seed Extract
  125. Effect Of Thermal Treatment Of Trepel At Temperature Range 800-1200˚C
  126. Topical Issue on Agriculture
  127. The effect of Cladophora glomerata exudates on the amino acid composition of Cladophora fracta and Rhizoclonium sp.
  128. Influence of the Static Magnetic Field and Algal Extract on the Germination of Soybean Seeds
  129. The use of UV-induced fluorescence for the assessment of homogeneity of granular mixtures
  130. The use of microorganisms as bio-fertilizers in the cultivation of white lupine
  131. Lyophilized apples on flax oil and ethyl esters of flax oil - stability and antioxidant evaluation
  132. Production of phosphorus biofertilizer based on the renewable materials in large laboratory scale
  133. Human health risk assessment of potential toxic elements in paddy soil and rice (Oryza sativa) from Ugbawka fields, Enugu, Nigeria
  134. Recovery of phosphates(V) from wastewaters of different chemical composition
  135. Special Issue on the 4th Green Chemistry 2018
  136. Dead zone for hydrogenation of propylene reaction carried out on commercial catalyst pellets
  137. Improved thermally stable oligoetherols from 6-aminouracil, ethylene carbonate and boric acid
  138. The role of a chemical loop in removal of hazardous contaminants from coke oven wastewater during its treatment
  139. Combating paraben pollution in surface waters with a variety of photocatalyzed systems: Looking for the most efficient technology
  140. Special Issue on Chemistry Today for Tomorrow 2019
  141. Applying Discriminant and Cluster Analyses to Separate Allergenic from Non-allergenic Proteins
  142. Chemometric Expertise Of Clinical Monitoring Data Of Prolactinoma Patients
  143. Chemomertic Risk Assessment of Soil Pollution
  144. New composite sorbent for speciation analysis of soluble chromium in textiles
  145. Photocatalytic activity of NiFe2O4 and Zn0.5Ni0.5Fe2O4 modified by Eu(III) and Tb(III) for decomposition of Malachite Green
  146. Photophysical and antibacterial activity of light-activated quaternary eosin Y
  147. Spectral properties and biological activity of La(III) and Nd(III) Monensinates
  148. Special Issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  149. Soil organic carbon mineralization in relation to microbial dynamics in subtropical red soils dominated by differently sized aggregates
  150. A potential reusable fluorescent aptasensor based on magnetic nanoparticles for ochratoxin A analysis
  151. Special Issue on 13th JCC 2018
  152. Fluorescence study of 5-nitroisatin Schiff base immobilized on SBA-15 for sensing Fe3+
  153. Thermal and Morphology Properties of Cellulose Nanofiber from TEMPO-oxidized Lower part of Empty Fruit Bunches (LEFB)
  154. Encapsulation of Vitamin C in Sesame Liposomes: Computational and Experimental Studies
  155. A comparative study of the utilization of synthetic foaming agent and aluminum powder as pore-forming agents in lightweight geopolymer synthesis
  156. Synthesis of high surface area mesoporous silica SBA-15 by adjusting hydrothermal treatment time and the amount of polyvinyl alcohol
  157. Review of large-pore mesostructured cellular foam (MCF) silica and its applications
  158. Ion Exchange of Benzoate in Ni-Al-Benzoate Layered Double Hydroxide by Amoxicillin
  159. Synthesis And Characterization Of CoMo/Mordenite Catalyst For Hydrotreatment Of Lignin Compound Models
  160. Production of Biodiesel from Nyamplung (Calophyllum inophyllum L.) using Microwave with CaO Catalyst from Eggshell Waste: Optimization of Transesterification Process Parameters
  161. The Study of the Optical Properties of C60 Fullerene in Different Organic Solvents
  162. Composite Material Consisting of HKUST-1 and Indonesian Activated Natural Zeolite and its Application in CO2 Capture
  163. Topical Issue on Environmental Chemistry
  164. Ionic liquids modified cobalt/ZSM-5 as a highly efficient catalyst for enhancing the selectivity towards KA oil in the aerobic oxidation of cyclohexane
  165. Application of Thermal Resistant Gemini Surfactants in Highly Thixotropic Water-in-oil Drilling Fluid System
  166. Screening Study on Rheological Behavior and Phase Transition Point of Polymer-containing Fluids produced under the Oil Freezing Point Temperature
  167. The Chemical Softening Effect and Mechanism of Low Rank Coal Soaked in Alkaline Solution
  168. The Influence Of NO/O2 On The NOx Storage Properties Over A Pt-Ba-Ce/γ-Al2O3 Catalyst
  169. Special Issue on the International conference CosCI 2018
  170. Design of SiO2/TiO2 that Synergistically Increases The Hydrophobicity of Methyltrimethoxysilane Coated Glass
  171. Antidiabetes and Antioxidant agents from Clausena excavata root as medicinal plant of Myanmar
  172. Development of a Gold Immunochromatographic Assay Method Using Candida Biofilm Antigen as a Bioreceptor for Candidiasis in Rats
  173. Special Issue on Applied Biochemistry and Biotechnology 2019
  174. Adsorption of copper ions on Magnolia officinalis residues after solid-phase fermentation with Phanerochaete chrysosporium
  175. Erratum
  176. Erratum to: Sand Dune Characterization For Preparing Metallurgical Grade Silicon
https://doi.org/10.1515/chem-2019-0028
Keywords for this article
osteosarcoma; velvet antler; growth factors; pathways; EMT
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Research on correlation of compositions with oestrogenic activity of Cistanche based on LC/Q-TOF-MS/MS technology
  3. Efficacy of Pyrus elaeagnifolia subsp. elaeagnifolia in acetic acid–induced colitis model
  4. Anti-inflammatory and antinociceptive features of Bryonia alba L.: As a possible alternative in treating rheumatism
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  6. Prediction of the Blood-Brain Barrier Permeability Using RP-18 Thin Layer Chromatography
  7. Phytic Acid Extracted from Rice Bran as a Growth Promoter for Euglena gracilis
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  9. Topological Indices of Hyaluronic Acid-Paclitaxel Conjugates’ Molecular Structure in Cancer Treatment
  10. Thermodynamic properties of the bubble growth process in a pool boiling of water-ethanol mixture two-component system
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  12. Characteristics of Stable Hydrogen and Oxygen Isotopes of Soil Moisture under Different Land Use in Dry Hot Valley of Yuanmou
  13. Specific, highly sensitive and simple spectrofluorimetric method for quantification of daclatasvir in HCV human plasma patients and in tablets dosage form
  14. Chromium-modified cobalt molybdenum nitrides as catalysts for ammonia synthesis
  15. Langerhans cell-like dendritic cells treated with ginsenoside Rh2 regulate the differentiation of Th1 and Th2 cells in vivo
  16. Identification of Powdery Mildew Blumeria graminis f. sp. tritici Resistance Genes in Selected Wheat Varieties and Development of Multiplex PCR
  17. Computational Analysis of new Degree-based descriptors of oxide networks
  18. The Use Of Chemical Composition And Additives To Classify Petrol And Diesel Using Gas Chromatography–Mass Spectrometry And Chemometric Analysis: A Uk Study
  19. Minimal Energy Tree with 4 Branched Vertices
  20. Jatropha seed oil derived poly(esteramide-urethane)/ fumed silica nanocomposite coatings for corrosion protection
  21. Calculating topological indices of certain OTIS interconnection networks
  22. Energy storage analysis of R125 in UIO-66 and MOF-5 nanoparticles: A molecular simulation study
  23. Velvet Antler compounds targeting major cell signaling pathways in osteosarcoma - a new insight into mediating the process of invasion and metastasis in OS
  24. Effects of Azadirachta Indica Leaf Extract, Capping Agents, on the Synthesis of Pure And Cu Doped ZnO-Nanoparticles: A Green Approach and Microbial Activity
  25. Aqueous Micro-hydration of Na+(H2O)n=1-7 Clusters: DFT Study
  26. A proposed image-based detection of methamidophos pesticide using peroxyoxalate chemiluminescence system
  27. Phytochemical screening and estrogenic activity of total glycosides of Cistanche deserticola
  28. Biological evaluation of a series of benzothiazole derivatives as mosquitocidal agents
  29. Chemical pretreatments of Trapa bispinosa's peel (TBP) biosorbent to enhance adsorption capacity for Pb(ll)
  30. Dynamic Changes in MMP1 and TIMP1 in the Antifibrotic Process of Dahuang Zhechong Pill in Rats with Liver Fibrosis
  31. The Optimization and Production of Ginkgolide B Lipid Microemulsion
  32. Photodynamic Therapy Enhanced the Antitumor Effects of Berberine on HeLa Cells
  33. Chiral and Achiral Enantiomeric Separation of (±)-Alprenolol
  34. Correlation of Water Fluoride with Body Fluids, Dental Fluorosis and FT4, FT3 –TSH Disruption among Children in an Endemic Fluorosis area in Pakistan
  35. A one-step incubation ELISA kit for rapid determination of dibutyl phthalate in water, beverage and liquor
  36. Free Radical Scavenging Activity of Essential Oil of Eugenia caryophylata from Amboina Island and Derivatives of Eugenol
  37. Effects of Blue and Red Light On Growth And Nitrate Metabolism In Pakchoi
  38. miRNA-199a-5p functions as a tumor suppressor in prolactinomas
  39. Solar photodegradation of carbamazepine from aqueous solutions using a compound parabolic concentrator equipped with a sun tracking system
  40. Influence of sub-inhibitory concentration of selected plant essential oils on the physical and biochemical properties of Pseudomonas orientalis
  41. Preparation and spectroscopic studies of Fe(II), Ru(II), Pd(II) and Zn(II) complexes of Schiff base containing terephthalaldehyde and their transfer hydrogenation and Suzuki-Miyaura coupling reaction
  42. Complex formation in a liquid-liquid extraction-chromogenic system for vanadium(IV)
  43. Synthesis, characterization (IR, 1H, 13C & 31P NMR), fungicidal, herbicidal and molecular docking evaluation of steroid phosphorus compounds
  44. Analysis and Biological Evaluation of Arisaema Amuremse Maxim Essential Oil
  45. A preliminary assessment of potential ecological risk and soil contamination by heavy metals around a cement factory, western Saudi Arabia
  46. Anti- inflammatory effect of Prunus tomentosa Thunb total flavones in LPS-induced RAW264.7 cells
  47. Collaborative Influence of Elevated CO2 Concentration and High Temperature on Potato Biomass Accumulation and Characteristics
  48. Methods of extraction, physicochemical properties of alginates and their applications in biomedical field – a review
  49. Characteristics of liposomes derived from egg yolk
  50. Preparation of ternary ZnO/Ag/cellulose and its enhanced photocatalytic degradation property on phenol and benzene in VOCs
  51. Influence of Human Serum Albumin Glycation on the Binding Affinities for Natural Flavonoids
  52. Synthesis and antioxidant activity of 2-methylthio-pyrido[3,2-e][1,2,4] triazolo[1,5-a]pyrimidines
  53. Comparative study on the antioxidant activities of ten common flower teas from China
  54. Molecular Properties of Symmetrical Networks Using Topological Polynomials
  55. Synthesis of Co3O4 Nano Aggregates by Co-precipitation Method and its Catalytic and Fuel Additive Applications
  56. Phytochemical analysis, Antioxidant and Antiprotoscolices potential of ethanol extracts of selected plants species against Echinococcus granulosus: In-vitro study
  57. Silver nanoparticles enhanced fluorescence for sensitive determination of fluoroquinolones in water solutions
  58. Simultaneous Quantification of the New Psychoactive Substances 3-FMC, 3-FPM, 4-CEC, and 4-BMC in Human Blood using GC-MS
  59. Biodiesel Production by Lipids From Indonesian strain of Microalgae Chlorella vulgaris
  60. Miscibility studies of polystyrene/polyvinyl chloride blend in presence of organoclay
  61. Antibacterial Activities of Transition Metal complexes of Mesocyclic Amidine 1,4-diazacycloheptane (DACH)
  62. Novel 1,8-Naphthyridine Derivatives: Design, Synthesis and in vitro screening of their cytotoxic activity against MCF7 cell line
  63. Investigation of Stress Corrosion Cracking Behaviour of Mg-Al-Zn Alloys in Different pH Environments by SSRT Method
  64. Various Combinations of Flame Retardants for Poly (vinyl chloride)
  65. Phenolic compounds and biological activities of rye (Secale cereale L.) grains
  66. Oxidative degradation of gentamicin present in water by an electro-Fenton process and biodegradability improvement
  67. Optimizing Suitable Conditions for the Removal of Ammonium Nitrogen by a Microbe Isolated from Chicken Manure
  68. Anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Haloxylon salicornicum aqueous fraction
  69. The anti-corrosion behaviour of Satureja montana L. extract on iron in NaCl solution
  70. Interleukin-4, hemopexin, and lipoprotein-associated phospholipase A2 are significantly increased in patients with unstable carotid plaque
  71. A comparative study of the crystal structures of 2-(4-(2-(4-(3-chlorophenyl)pipera -zinyl)ethyl) benzyl)isoindoline-1,3-dione by synchrotron radiation X-ray powder diffraction and single-crystal X-ray diffraction
  72. Conceptual DFT as a Novel Chemoinformatics Tool for Studying the Chemical Reactivity Properties of the Amatoxin Family of Fungal Peptides
  73. Occurrence of Aflatoxin M1 in Milk-based Mithae samples from Pakistan
  74. Kinetics of Iron Removal From Ti-Extraction Blast Furnace Slag by Chlorination Calcination
  75. Increasing the activity of DNAzyme based on the telomeric sequence: 2’-OMe-RNA and LNA modifications
  76. Exploring the optoelectronic properties of a chromene-appended pyrimidone derivative for photovoltaic applications
  77. Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome
  78. Cyclodextrin potentiometric sensors based on selective recognition sites for procainamide: Comparative and theoretical study
  79. Greener synthesis of dimethyl carbonate from carbon dioxide and methanol using a tunable ionic liquid catalyst
  80. Nonisothermal Cold Crystallization Kinetics of Poly(lactic acid)/Bacterial Poly(hydroxyoctanoate) (PHO)/Talc
  81. Enhanced adsorption of sulfonamide antibiotics in water by modified biochar derived from bagasse
  82. Study on the Mechanism of Shugan Xiaozhi Fang on Cells with Non-alcoholic Fatty Liver Disease
  83. Comparative Effects of Salt and Alkali Stress on Antioxidant System in Cotton (Gossypium Hirsutum L.) Leaves
  84. Optimization of chromatographic systems for analysis of selected psychotropic drugs and their metabolites in serum and saliva by HPLC in order to monitor therapeutic drugs
  85. Electrocatalytic Properties of Ni-Doped BaFe12O19 for Oxygen Evolution in Alkaline Solution
  86. Study on the removal of high contents of ammonium from piggery wastewater by clinoptilolite and the corresponding mechanisms
  87. Phytochemistry and toxicological assessment of Bryonia dioica roots used in north-African alternative medicine
  88. The essential oil composition of selected Hemerocallis cultivars and their biological activity
  89. Mechanical Properties of Carbon Fiber Reinforced Nanocrystalline Nickel Composite Electroforming Deposit
  90. Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis
  91. Topical Issue on Applications of Mathematics in Chemistry
  92. Zagreb Connection Number Index of Nanotubes and Regular Hexagonal Lattice
  93. The Sanskruti index of trees and unicyclic graphs
  94. Valency-based molecular descriptors of Bakelite network BNmn
  95. Computing Topological Indices for Para-Line Graphs of Anthracene
  96. Zagreb Polynomials and redefined Zagreb indices of Dendrimers and Polyomino Chains
  97. Topological Descriptor of 2-Dimensional Silicon Carbons and Their Applications
  98. Topological invariants for the line graphs of some classes of graphs
  99. Words for maximal Subgroups of Fi24‘
  100. Generators of Maximal Subgroups of Harada-Norton and some Linear Groups
  101. Special Issue on POKOCHA 2018
  102. Influence of Production Parameters on the Content of Polyphenolic Compounds in Extruded Porridge Enriched with Chokeberry Fruit (Aronia melanocarpa (Michx.) Elliott)
  103. Effects of Supercritical Carbon Dioxide Extraction (SC-CO2) on the content of tiliroside in the extracts from Tilia L. flowers
  104. Impact of xanthan gum addition on phenolic acids composition and selected properties of new gluten-free maize-field bean pasta
  105. Impact of storage temperature and time on Moldavian dragonhead oil – spectroscopic and chemometric analysis
  106. The effect of selected substances on the stability of standard solutions in voltammetric analysis of ascorbic acid in fruit juices
  107. Determination of the content of Pb, Cd, Cu, Zn in dairy products from various regions of Poland
  108. Special Issue on IC3PE 2018 Conference
  109. The Photocatalytic Activity of Zns-TiO2 on a Carbon Fiber Prepared by Chemical Bath Deposition
  110. N-octyl chitosan derivatives as amphiphilic carrier agents for herbicide formulations
  111. Kinetics and Mechanistic Study of Hydrolysis of Adenosine Monophosphate Disodium Salt (AMPNa2) in Acidic and Alkaline Media
  112. Antimalarial Activity of Andrographis Paniculata Ness‘s N-hexane Extract and Its Major Compounds
  113. Special Issue on ABB2018 Conference
  114. Special Issue on ICCESEN 2017
  115. Theoretical Diagnostics of Second and Third-order Hyperpolarizabilities of Several Acid Derivatives
  116. Determination of Gamma Rays Efficiency Against Rhizoctonia solani in Potatoes
  117. Studies On Compatibilization Of Recycled Polyethylene/Thermoplastic Starch Blends By Using Different Compatibilizer
  118. Liquid−Liquid Extraction of Linalool from Methyl Eugenol with 1-Ethyl-3-methylimidazolium Hydrogen Sulfate [EMIM][HSO4] Ionic Liquid
  119. Synthesis of Graphene Oxide Through Ultrasonic Assisted Electrochemical Exfoliation
  120. Special Issue on ISCMP 2018
  121. Synthesis and antiproliferative evaluation of some 1,4-naphthoquinone derivatives against human cervical cancer cells
  122. The influence of the grafted aryl groups on the solvation properties of the graphyne and graphdiyne - a MD study
  123. Electrochemical modification of platinum and glassy carbon surfaces with pyridine layers and their use as complexing agents for copper (II) ions
  124. Effect of Electrospinning Process on Total Antioxidant Activity of Electrospun Nanofibers Containing Grape Seed Extract
  125. Effect Of Thermal Treatment Of Trepel At Temperature Range 800-1200˚C
  126. Topical Issue on Agriculture
  127. The effect of Cladophora glomerata exudates on the amino acid composition of Cladophora fracta and Rhizoclonium sp.
  128. Influence of the Static Magnetic Field and Algal Extract on the Germination of Soybean Seeds
  129. The use of UV-induced fluorescence for the assessment of homogeneity of granular mixtures
  130. The use of microorganisms as bio-fertilizers in the cultivation of white lupine
  131. Lyophilized apples on flax oil and ethyl esters of flax oil - stability and antioxidant evaluation
  132. Production of phosphorus biofertilizer based on the renewable materials in large laboratory scale
  133. Human health risk assessment of potential toxic elements in paddy soil and rice (Oryza sativa) from Ugbawka fields, Enugu, Nigeria
  134. Recovery of phosphates(V) from wastewaters of different chemical composition
  135. Special Issue on the 4th Green Chemistry 2018
  136. Dead zone for hydrogenation of propylene reaction carried out on commercial catalyst pellets
  137. Improved thermally stable oligoetherols from 6-aminouracil, ethylene carbonate and boric acid
  138. The role of a chemical loop in removal of hazardous contaminants from coke oven wastewater during its treatment
  139. Combating paraben pollution in surface waters with a variety of photocatalyzed systems: Looking for the most efficient technology
  140. Special Issue on Chemistry Today for Tomorrow 2019
  141. Applying Discriminant and Cluster Analyses to Separate Allergenic from Non-allergenic Proteins
  142. Chemometric Expertise Of Clinical Monitoring Data Of Prolactinoma Patients
  143. Chemomertic Risk Assessment of Soil Pollution
  144. New composite sorbent for speciation analysis of soluble chromium in textiles
  145. Photocatalytic activity of NiFe2O4 and Zn0.5Ni0.5Fe2O4 modified by Eu(III) and Tb(III) for decomposition of Malachite Green
  146. Photophysical and antibacterial activity of light-activated quaternary eosin Y
  147. Spectral properties and biological activity of La(III) and Nd(III) Monensinates
  148. Special Issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  149. Soil organic carbon mineralization in relation to microbial dynamics in subtropical red soils dominated by differently sized aggregates
  150. A potential reusable fluorescent aptasensor based on magnetic nanoparticles for ochratoxin A analysis
  151. Special Issue on 13th JCC 2018
  152. Fluorescence study of 5-nitroisatin Schiff base immobilized on SBA-15 for sensing Fe3+
  153. Thermal and Morphology Properties of Cellulose Nanofiber from TEMPO-oxidized Lower part of Empty Fruit Bunches (LEFB)
  154. Encapsulation of Vitamin C in Sesame Liposomes: Computational and Experimental Studies
  155. A comparative study of the utilization of synthetic foaming agent and aluminum powder as pore-forming agents in lightweight geopolymer synthesis
  156. Synthesis of high surface area mesoporous silica SBA-15 by adjusting hydrothermal treatment time and the amount of polyvinyl alcohol
  157. Review of large-pore mesostructured cellular foam (MCF) silica and its applications
  158. Ion Exchange of Benzoate in Ni-Al-Benzoate Layered Double Hydroxide by Amoxicillin
  159. Synthesis And Characterization Of CoMo/Mordenite Catalyst For Hydrotreatment Of Lignin Compound Models
  160. Production of Biodiesel from Nyamplung (Calophyllum inophyllum L.) using Microwave with CaO Catalyst from Eggshell Waste: Optimization of Transesterification Process Parameters
  161. The Study of the Optical Properties of C60 Fullerene in Different Organic Solvents
  162. Composite Material Consisting of HKUST-1 and Indonesian Activated Natural Zeolite and its Application in CO2 Capture
  163. Topical Issue on Environmental Chemistry
  164. Ionic liquids modified cobalt/ZSM-5 as a highly efficient catalyst for enhancing the selectivity towards KA oil in the aerobic oxidation of cyclohexane
  165. Application of Thermal Resistant Gemini Surfactants in Highly Thixotropic Water-in-oil Drilling Fluid System
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  167. The Chemical Softening Effect and Mechanism of Low Rank Coal Soaked in Alkaline Solution
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  175. Erratum
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