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In vitro apoptotic effect of Zinc(II) complex with N-donor heterocyclic ligand on breast cancer cells

  • Gamze Guney Eskiler ORCID logo EMAIL logo and Ibrahim Kani
Published/Copyright: July 19, 2019
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Turkish Journal of Biochemistry
From the journal Turkish Journal of Biochemistry Volume 44 Issue 6

Abstract

Background

The synthesis of new ligand and transition metal complexes have drawn great attention in cancer treatment due to excellent DNA cleavage activities and high antitumor activity.

Objective

The purpose of this study was to synthesize a new Zn(II) complex with 2,2′-bipyridine (bpy) ligand, [Zn(bpy)2(H2O)]2(ClO4), and to investigate the potential therapeutic activity against breast cancer.

Materials and methods

Zn(II) complex was obtained and structurally characterized using crystallography and other spectroscopic methods. The cytotoxic and apoptotic effects of Zn(II) complex on MCF7 breast cancer and HUVEC control cells were evaluated by WST-1, Annexin V and cell cycle analysis.

Results

The spectroscopic data demonstrated that Zn(II) complex was successfully synthesized. Furthermore, Zn(II) complex exhibited significant cytotoxic effect on MCF7 breast cancer and HUVEC cells (p < 0.01). MCF7 and HUVEC cells proliferation was reduced to 11.0% and 52.6%, respectively at 10 μM for 48 h. Additionally, Zn(II) complex significantly induced apoptotic cell death (84.87%) and caused S phase arrest (36.4%) in MCF7 cells at 10 μM (p < 0.01).

Conclusions

Zn(II) complex has great therapeutic potential for the treatment of breast cancer. However, further studies are warranted to identify the underlying mechanisms of apoptotic cell death and to reduce the toxicity of Zn(II) complex on control cells.

Öz

Amaç

Yeni ligand ve geçiş metali komplekslerinin sentezi, DNA kırılması aktiviteleri ve yüksek antitümör aktivitesi nedeniyle kanser tedavisinde önemli derecede dikkat çekmektedir. Bu çalışmanın amacı 2,2′-bipiridin (bpy) ligandı, [Zn(bpy)2(H2O)]2(ClO4) ile yeni bir Zn(II) kompleksi sentezlemek ve meme kanserinde potansiyel terapötik etkisinin araştırılmasıdır.

Gereç ve Yöntem

Zn(II) kompleksi elde edildikten sonra yapısal olarak kristalografi ve diğer spektroskopik yöntemler kullanılarak karakterize edilmiştir. Zn(II) kompleksinin MCF7 meme kanseri ve HUVEC kontrol hücreleri üzerindeki sitotoksik ve apoptotik etkileri, WST-1, Annexin V ve hücre döngüsü analizi ile değerlendirilmiştir.

Bulgular

Spektroskopik veriler, Zn(II) kompleksinin başarıyla sentezlendiğini göstermektedir. Zn(II) kompleksi, MCF7 meme kanseri ve HUVEC hücreleri üzerinde önemli sitotoksik etki göstermiştir (p < 0.01). 48 saat boyunca 10 μM Zn(II) kompleksi uygulanan MCF7 ve HUVEC hücrelerinde canlılık oranlarının sırasıyla %11.0 ve %52.6’ya azaldığı belirlenmiştir. Ayrıca, 10 μM Zn(II) kompleksi MCF7 hücrelerinde apoptotik hücre ölümünü (%84.87) önemli ölçüde arttırmıştır ve hücrelerde S fazında tutulmaya (%36.4) neden olmuştur (p < 0.01).

Sonuç

Zn(II) kompleksinin, meme kanseri tedavisinde önemli terapötik potansiyele sahip olduğu belirlenmiştir. Ancak, apoptotik hücre ölümüne neden olan mekanizmaları tanımlamak ve Zn(II) kompleksinin kontrol hücreleri üzerindeki toksisitesini azaltmak için ileri çalışmaların yapılması gereklidir.

Keywords: Metal complex; Zinc; 2,2′-Bipyridine; Breast cancer; Apoptosis
Anahtar kelimeler: Metal kompleks; Çinko; 2,2′-bipiridin; Meme kanseri; Apoptoz

Introduction

Metal complexes have received considerable attention in the treatment of cancer due to their ability to induce catalytic processes, to provide higher selectivity and to exhibit a broader spectrum of biological activity [1], [2], [3]. Zinc(II) is an essential trace element that requires for the functionality of more than 300 enzymes and immune system, the stabilization of DNA, gene expression, cell proliferation, etc. Zn(II)-based hydrolytic cleavage promises therapeutic potential in cancer treatment due to its low toxicity, redox inertness, hard Lewis acid character and good biocompatibility of Zn ions [4], [5].

In the literature, different Zn(II) complexes have been synthesized and the anti-proliferative effects of these complex on different cancer cells (prostate, breast and lung) have been determined [6], [7], [8], [9], [10]. Furthermore, there is an evidence that Zn may play role in carcinogenesis depending the dose and cell type. For example, decreasing in cellular Zn levels may be the risk factors for breast, prostate and ovarian cancer, pancreatic adenocarcinoma and hepatocellular carcinoma [11], [12], [13]. In this context, new zinc-ligand modifications have received much attention in recent years. For this purpose, we prepared a [Zn(bpy)2(H2O)]2(ClO4) complex and characterized with single crystal X-ray, FT-IR and UV-vis. Finally, the therapeutic effects of Zn(II) complex on MCF7 breast cancer and human umbilical vein endothelial cells (HUVEC) were investigated.

Materials and methods

Synthesis of [Zn(bpy)2(H2O)]2(ClO4)

To a solution of 2,2′-bipyridine ligand (0.940 g, 0.60 mmol) in methanol (10 mL) was added a solution of Zn(ClO4)2·6(H2O) (0.100 g, 0.27 mmol) in methanol (15 mL). The mixture was stirred at 60°C temperature for 6 h. After the mixture was filtered, slow evaporation at room temperature afforded colorless crystals. Yield 0.136 g (85% based on Zn). M.p. 255°C Anal. Calc. for C12H10Cl2N2Zn: C, 40.40; H, 3.05; N, 9.42. Found: C, 40.62; H, 3.12; N, 9.49%. IR [(KBr, ν cm−1)] selected bonds: ν(O–H) water 3200–3400 (b), ν(C–H) 3060(m), ν(C=C), ν(C=N) 1600(s), 1554(m), and ν(ClO4) 1089 (vs.), 625 (s). UV–Vis λmax nm (CH3CN): 198, 243, 297 and 308.

Determination of X-ray structure

Crystals of Zn(II) complex for X-ray crystal-structure were obtained by slow evaporation. The data for complex was measured at room temperature on a Bruker ApexII area-detector diffractometer using Mo Kα radiation (λ=0.71073 Å) from a fine-focus X-ray. The data collection and refinement parameters were summarized in Table 1. Data reduction was performed using the Bruker SMART program package [14]. The structure was solved by direct methods using SHELXS97 and refined SHELXL-2014 [15]. The molecular structure was visualized by MERCURY [16]. PLATON was used for geometric calculations [17].

Table 1:

Crystal data and structure refinement for complex.

Empirical formulaC40 H36 Cl4 N8 O18 Zn2
Formula weight1189.31
Temperature108(2) K
Wavelength0.71073 Å
Crystal system, space groupMonoclinic, P 21/n
Unit cell dimensionsa=9.0137(3) Å,   α=90°
b=12.9132(5) Å,   β=101.4730(10)°
c=19.6330(7) Å,   γ=90°
Volume2239.54(14) Å3
Z, calculated density2, 1.764 Mg/m3
Absorption coefficient1.398 mm−1
F(000)1208
Crystal size0.29×0.20×0.12 mm
Theta range for data collection1.90–28.40°
Limiting indices−8≤h≤12, −17≤k≤13, −20≤l≤22
Reflections collected/unique11,829/4469 [R(int)=0.0226]
Absorption correctionSemi-empirical from equivalents
Max. and min. transmission0.8502 and 0.6873
Refinement methodFull-matrix least-squares on F2

Cell culture

MCF7 and HUVEC cell lines were purchased from ATCC. MCF7 breast cancer and Human umbilical vein endothelial cell (HUVEC) lines were maintained in a humidified incubator at 37°C with 5% CO2. These cells were grown in Dulbecco’s Modified Eagle’s Medium (DMEM), containing 10% fetal bovine serum (FBS) and penicillin (100 U/mL) and streptomycin (100 μg/mL).

WST-1 assay

The cytotoxic effects of Zn(II) complex on MCF7 and HUVEC cells were assessed by WST-1 assay (BioVision, San Francisco, CA, USA). Briefly, MCF7 and HUVEC cells (2×104 cells/well) were treated with Zn(II) complex at various concentrations (1.25, 2.5, 5, 7.5, 10, 25 and 50 μM) for 24 and 48 h. Then, 10 μL/well of the WST-1 reagent was added. After incubation for 1–3 h, the absorption at 450 nm was measured using an Elisa reader (Allsheng, China).

Annexin V analysis

To determine the effect of Zn(II) complex on apoptotic cell death, the minimum (1.25 μM) and the maximum (10 μM) concentration were selected as a similar inhibition rate was observed at 25 and 50 μM in MCF7 cells according to WST-1 results. To analyze the apoptotic effect of Zn(II) complex, MCF7 cells were seeded into 6-well plates (1×105 cells/well) and treated with Zn(II) complex. After 48 h of incubation, cells were trypsinized, stained with Muse Annexin V and Dead Cell Assay Kit (Millipore, Darmstadt, Germany) and analyzed with Muse Cell Analyzer (Muse™ EMD Millipore Co., Hayward, CA, USA) (n=3). Additionally, the apoptotic effects of 1.25 and 10 μM of Zn(II) complex was further confirmed by Multi Caspase Assay (Millipore, Darmstadt, Germany) including caspase-1, 3, 4, 5, 6, 7, 8, and 9 activity according to manufacturer protocol and analyzed by Muse Cell Analyzer (Muse™ EMD Millipore Co., Hayward, CA, USA) (n=3).

Cell cycle analysis

To analyze the effects of Zn(II) complex on the G0/G1, S and G2/M arrest, MCF7 cells were seeded into 6-well plates (5×105 cells/well) and treated with 1.25 and 10 μM concentrations of Zn(II) complex for 48 h. After fixation with cold 70% ethanol for at least 3 h, the cells were stained with Muse Cell Cycle Assay Kit (Millipore) for 30 min in the dark and each group was analyzed by Muse Cell Analyzer (Muse™ EMD Millipore Co., Hayward, CA, USA) (n=3).

Statistical analysis

SPSS 22.0 software was used for all statistical analysis. A one-way analysis of variance (ANOVA) and post-hoc test were carried out to determine the differences between the means of three or more independent groups. *p<0.05 and **p<0.01 were considered statistically significant.

Results

Structural description of the complex

The perspective view of the structure along with the crystallographic numbering was shown in Figure 1A. The crystallographic data and some selected bond lengths and angles were summarized in Tables 1 and 2. XRD data demonstrated that the complex was monoclinic crystal system with space group P 21/n. The Zn(II) complex contained two molecules of bpy and one molecule of water. The metal ion was coordinated by four N (N1, N2, N3 or N4) from two bpy, one O (O5) from water molecule. The coordination geometry may be approximated as a strongly distorted trigonal bipyramid in which the Zn, N1, N4 and O5 atoms defined the basal trigonal plane and the N2 and N3 atoms occupied apical positions (Figure 1A). The N-Zn-N angle was the widest (N2ZnN3=178.82) and the equatorial region angles were in the range of 121.14–118.36 deviating from 120°. The bite angle of bpy ligands were in the range of 78.83°–102.45°. The axial bond distances between N-Zn (N1-Zn=2.0693 Å and N4-Zn=2.0646 Å) was longer than equatorial N-Zn distances (N2-Zn=2.0993 Å and N3-Zn=2.0858 Å). The bond length of Zn-N was similar to analogues published structures [18], [19], [20], [21], [22]. The bpy ligands were almost planer [torsion angle (N1C5C6N2=0.1° (2) and N3C11C16N4=0.7° (2)]. The uncoordinated perchlorate molecules link adjacent complexes through hydrogen bonds with coordinated water molecule. In the unit cell structure, mononuclear units were linked by two O–H…O hydrogen bonds between O-H of the coordinated water molecule and oxygen atoms of perchlorate ion, with an O5…O2 distance of 2.935 (2) Å (O5-H21A…O2) and O5…O6 distance of 2.746 (2) Å (O5-H21B…O6) (Figure 1B).

Figure 1: (A) Trigonal bipyramidal molecular structure of Zn(II) complex with 2,2′-bipyridine ligand. (B) Hydrogen bonding interactions between uncoordinated perchlorate and coordinated water molecule (O5…O2 distance of 2.935 (2) Å (O5-H21A…O2) and O5…O6 distance of 2.746 (2) Å (O5-H21B…O6).
Figure 1:

(A) Trigonal bipyramidal molecular structure of Zn(II) complex with 2,2′-bipyridine ligand. (B) Hydrogen bonding interactions between uncoordinated perchlorate and coordinated water molecule (O5…O2 distance of 2.935 (2) Å (O5-H21A…O2) and O5…O6 distance of 2.746 (2) Å (O5-H21B…O6).

Table 2:

Some selected bond lengths (Å) and bond angles (°) for Zn(II) complex.

Zn1-O52.0502(16)O5-Zn1-N1120.50(7)
Zn1-N12.0692(17)O5-Zn1-N290.64(6)
Zn1-N22.0993(16)O5-Zn1-N388.80(6)
Zn1-N32.0859(16)O5-Zn1-N4121.14(7)
Zn1-N42.0647(16)N1-Zn1-N278.73(6)
N4-Zn1-N1118.36(6)N1-Zn1-N3102.45(6)
N4-Zn1-N2100.28(6)N3-Zn1-N2178.82(7)

The IR spectra of the complex demonstrated two bands at 1089 cm−1 and 625 cm−1, an indication of the perchlorate anion. A broad absorption band centered at 3433 cm−1 due to the νsym/asym vibration of the OH group in the water molecule. The bands of around 1600 cm−1 and 767 cm−1 were observed due to the νbpy vibration of bpy ligand. The UV spectrum of the complex in acetonitrile showed that the lower wavelength bands maximum absorptions at 198–308 nm may be assigned to π–π* transitions of the aromatic rings and the charge transfer band to ligand from metal (MLCT) [23].

Zn(II) complex inhibits the proliferation of breast cancer cells

The anti-proliferative effects of Zn(II) complex on the viability of MCF7 and HUVEC cells were determined by WST-1 assay (Figure 2). As shown in Figure 2A, MCF7 cell viability significantly decreased to 40.9%, 11.0% and 12.2% at a concentration of 1.25, 10 and 50 μM Zn(II) complex (p<0.01), respectively for 48 h. However, the viability of HUVEC cells considerably reduced to 42.3%, 52.6% and 40.7% at a concentration of 1.25, 10 and 50 μM Zn(II) complex, respectively for 48 h (p<0.01, Figure 2B). Therefore, an inhibitory effect of Zn(II) complex on MCF7 proliferation was detected in a dose and time-dependent manner.

Figure 2: The anti-proliferative effects of Zn(II) complex on the viability of MCF7 and HUVEC cells were determined by WST-1 assay.The viability of (A) MCF7 breast cancer and (B) HUVEC cells after 24 and 48 h exposure to 1.25, 2.5, 5, 7.5, 10, 25 and 50 μM Zn(II) complex (**p<0.01).
Figure 2:

The anti-proliferative effects of Zn(II) complex on the viability of MCF7 and HUVEC cells were determined by WST-1 assay.

The viability of (A) MCF7 breast cancer and (B) HUVEC cells after 24 and 48 h exposure to 1.25, 2.5, 5, 7.5, 10, 25 and 50 μM Zn(II) complex (**p<0.01).

Zn(II) complex induces apoptosis in breast cancer cells

To reveal a possible apoptotic inducing effect of Zn(II) complex on MCF7 breast cancer cells, we carried out Annexin V assay and our findings were summarized in Figure 3. At a concentration of 1.25 and 10 μM Zn(II) complex, the percentage of total apoptotic cells was 50.45% and 84.87%, respectively for 48 h. Thus, the total number of apoptotic cells remarkably increased 13.8- and 23.2-fold, respectively (p<0.01) as compared with control cells. Furthermore, we explored the activity of apoptotic cell death by multi-caspase assay (Figure 3). After incubation with 1.25 and 10 μM Zn(II) complex, the rate of caspase positive/dead cells was 23.44% and 69.89%, respectively in MCF-7 cells (p<0.01). Thus, Zn(II) complex significantly induced apoptotic cell death through multi-caspase activity in breast cancer cells.

Figure 3: The apoptotic effect of Zn(II) complex on MCF7 cells was determined by Annexin V analysis.(A) The results of Annexin V and multi-caspase analysis. (B) Statistical analysis of the results of total apoptotic cells after treatment with different concentrations of Zn(II) complex (p<0.01**).
Figure 3:

The apoptotic effect of Zn(II) complex on MCF7 cells was determined by Annexin V analysis.

(A) The results of Annexin V and multi-caspase analysis. (B) Statistical analysis of the results of total apoptotic cells after treatment with different concentrations of Zn(II) complex (p<0.01**).

Zn(II) complex induces cell cycle arrest

To explore the effects of Zn(II) complex on cell cycle arrest, the cells were stained with cell cycle assay. As shown in Figure 4, Zn(II) complex caused a remarkable increase in the percentage of S phase (from 11.3% to 29.7% and 36.4%) at a concentration of 1.25 and 10 μM Zn(II) complex, respectively (p<0.01). Furthermore, the proportion of MCF7 cells in G0/G1 arrest decreased from 45.0% to 41.2% and 28.6% at a concentration of 1.25 and 10 μM Zn(II) complex, respectively. Thus, Zn(II) complex significantly caused at S phase arrest in MCF7 cells.

Figure 4: Effects of Zn(II) complex on cell cycle distribution in MCF7 cells.(A) The results of cell cycle analysis. (B) Statistical analysis of the results of cell cycle distribution after treatment with different concentrations of Zn(II) complex (p<0.01**).
Figure 4:

Effects of Zn(II) complex on cell cycle distribution in MCF7 cells.

(A) The results of cell cycle analysis. (B) Statistical analysis of the results of cell cycle distribution after treatment with different concentrations of Zn(II) complex (p<0.01**).

Discussion

In the current study, we evaluated that a new Zn(II) complex successfully synthesized, characterized and significantly inhibited the proliferation of MCF7 breast cancer cells through induction of apoptosis and S phase arrest. On the other hand, Zn(II) complex exhibited toxic effects on control cells. Thus, there is an urgent need to improve new strategies for reducing undesirable effects of metal-ligand complexes on control cells.

Transition metals complexes with different ligands have provided cancer research with new insights to overcome the limitations of current chemotherapeutic agents. In this context, utilization of different transition metals (Mn, Fe, Cu, Co, Au and others, etc.) and their complexes have increasing attention for cancer treatment due to their anticancer activity. In the literature, different Zn complex (tetranuclear Zn complex [Zn4(μ3−OH)2(PiCO)6(H2O)4], Zn(L)(OAc)·3H2O, Zn(L)2·2H2O, phosphido pincer-Zn(II) complexes [(PPP)ZnR], divinylzinc Zn complexes (Zn[C(Me)=CH2]2 and Zn[C(H)=CMe2]2), Zn(II) with 4,4′-bipyridine complex, Zn3(μ3-PO4) and Zn3(μ3-CO3), etc.] have been synthesized and structurally characterized [24], [25], [26], [27], [28], [29]. However, there has been limited studies to assess the anticancer effects of Zn complexes on cancer cells. Milacic et al. found that pyrrolidine dithiocarbamate (PyDT)-zinc(II) complex induced apoptotic cell death by calpain activation in human breast (MDA-MB-231) and prostate cancer cell lines (PC-3) [7]. Cui et al. stated that two zinc(II) {[Zn(bibp)(MoO4)](H2O)2}n [bibp=4,4′-bis(imidazol-1-yl)-biphenyl] and nickel(II) based coordination polymers exhibited anticancer activity on MDA-MB-231, MDA-MB-468, SK-BR-3, and MCF7 breast cancer cells [8]. Rundstadler et al. reported that zinc(II)-phenanthroline-indomethacin complexes could kill breast cancer stem cells and bulk breast cancer cells [9]. In the current study, a novel Zn(II) complex remarkably inhibited MCF7 cell proliferation by inducing apoptotic cell death and cell accumulation in the S phase. However, the underlying molecular mechanisms of Zn(II)-based apoptotic cell death need to be explored.

Furthermore, only one study, to our knowledge, investigated the potential cytotoxic and apoptotic effects of Zn-S-NVC complex on PC3 human prostate cancer and PNT1A human normal prostate epithelium cell lines [10]. They found that Zn-S complex and NVC induced high toxicity in both PC3 and PNT1A. However, Zn-S-NVC complex reduced the PC3 cell viability by 65% without damage to PNT1A control cells [10]. Thus, the cytotoxic and apoptotic effects of transition metal-complexes on control cell lines should be determined to provide information on the exact potential anticancer activities. In our study, Zn(II) complex inhibited the proliferation of HUVEC control cells. Therefore, there is need for discovery of new Zn complexes with different ligands to reduce the toxic side effects on control cells.

Consequently, Zn(II) complex coordinated with bpy ligand significantly suppress breast cancer cell growth in a dose-dependent manner and induce cell cycle arrest and apoptotic cell death. However, further studies are needed to identify the mechanism underlying its apoptotic effect and to reduce toxicity on control cells. Additionally, metal-based drug design studies could include in vitro experiments with cancer and control cell lines to assess therapeutic effects and toxicity of metal complexes on cancer therapy.

Supplementary material

CCDC 860726 contains the supplementary crystallographic data for Zn(II) complex. These data can be downloaded via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: .

Acknowledgments

The authors would like to acknowledge the support from the Medicinal Plants and Medicine Research Centre of Anadolu University, Eskişehir, Turkey for the use of X-ray Diffractometer.

  1. Conflicts of interest: The authors declare that they have no conflicts of interest.

References

1. Ndagi U, Mhlongo N, Soliman ME. Metal complexes in cancer therapy – an update from drug design perspective. Drug Des Devel Ther 2017;11:599.10.2147/DDDT.S119488Search in Google Scholar PubMed PubMed Central

2. Baile MB, Kolhe NS, Deotarse PP, Jain AS, Kulkarni AA. Metal ion complex-potential anticancer drug – a review. Int. J Pharm Sci Rev Res 2015;4:59–66.Search in Google Scholar

3. Rafique S, Idrees M, Nasim A, Akbar H, Athar A. Transition metal complexes as potential therapeutic agents. Biotechnol Mol Biol Rev 2010;5:38–45.Search in Google Scholar

4. Liguori PF, Valentini A, Palma M, Bellusci A, Bernardini S, Ghedini M, et al. Non-classical anticancer agents: synthesis and biological evaluation of zinc(II) heteroleptic complexes. Dalton Trans 2010;39:4205–12.10.1039/b922101hSearch in Google Scholar PubMed

5. Komiyama M, Takeda N, Shigekawa H. Hydrolysis of DNA and RNA by lanthanide ions: mechanistic studies leading to new applications. Chem Commun 1999;16:1443–51.10.1039/a901621jSearch in Google Scholar

6. Niittymäki T, Lönnberg H. Artificial ribonucleases. Org Biomol Chem 2006;4:15–25.10.1039/B509022ASearch in Google Scholar PubMed

7. Milacic V, Chen D, Giovagnini L, Diez A, Fregona D, Dou QP. Pyrrolidine dithiocarbamate-zinc(II) and-copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity. Toxicol Appl Pharmacol 2008;231:24–33.10.1016/j.taap.2008.03.009Search in Google Scholar PubMed PubMed Central

8. Cui LJ, Zhang B, Liu CY, Bian M. Two Zinc(II) and Nickel(II)-based complexes: anti breast cancer activity. Z Anorg Allg Chem 2017;643:1139–42.10.1002/zaac.201700190Search in Google Scholar

9. Rundstadler T, Eskandari A, Norman S, Suntharalingam K. Polypyridyl Zinc(II)-indomethacin complexes with potent anti-breast cancer stem cell activity. Molecules 2018;23:2253.10.3390/molecules23092253Search in Google Scholar PubMed PubMed Central

10. Milosavljevic V, Haddad Y, Rodrigo MA, Moulick A, Polanska H, Hynek D, et al. The Zinc-Schiff base-novicidin complex as a potential prostate cancer therapy. PLoS One 2016;11:e0163983.10.1371/journal.pone.0163983Search in Google Scholar PubMed PubMed Central

11. Frezza M, Hindo S, Chen D, Davenport A, Schmitt S, Tomco D, et al. Novel metals and metal complexes as platforms for cancer therapy. Curr Pharm Des 2010;16:1813–25.10.2174/138161210791209009Search in Google Scholar PubMed PubMed Central

12. Fukuda H, Ebara M, Yamada H, Arimoto M, Okabe S, Obu M, et al. Trace elements and cancer. Japan Med Assoc J 2004;47:391–5.Search in Google Scholar

13. Franklin RB, Costello LC. The important role of the apoptotic effects of zinc in the development of cancers. J Cell Biochem 2009;106:750–7.10.1002/jcb.22049Search in Google Scholar PubMed PubMed Central

14. Sheldrick GM. Smart Bruker AXS. Inc., Madison, WI, USA, 2000.Search in Google Scholar

15. Sheldrick GM. SHELXS-2014, program for the crystal structure solution. Göttingen, Germany: University of Göttingen, 2014.Search in Google Scholar

16. Macrae CF, Edgington PR, McCabe P, Pidcock E, Shields GP, Taylor R, et al. Mercury: visualization and analysis of crystal structures. J Appl Cryst 2006;39:453.10.1107/S002188980600731XSearch in Google Scholar

17. Spek AL. Tool PAMC. Multipurpose crystallographic tool. Utrecht University, Utrecht, The Netherlands, 2003 and updates. J Appl Crystallogr 2003;36:7–13.10.1107/S0021889802022112Search in Google Scholar

18. Spek AL. Acta Crystallogr D 2009;65:148–55.10.1107/S090744490804362XSearch in Google Scholar

19. Lee YJ, Kim EY, Kim SH, Jang SP, Lee TG, Kim C, et al. Synthesis, crystal structures, photoluminescence, and catalytic reactivity of novel coordination polymers (0-D, 1-D, 2-D to 3-D) constructed from cis-1,2-cyclohexanedicarboxylic acid and various bipyridyl ligands. New J Chem 2011;35:833–41.10.1039/c0nj00869aSearch in Google Scholar

20. Baitalik S, Flörke U, Nag K. Homo-and heterobimetallic complexes of ruthenium(II) and osmium(II) with pyrazole-3, 5-dicarboxylic acid and 2,2′-bipyridine as co-ligands. Synthesis, structure, stereochemistry, spectroscopy and redox activities. Inorg Chim Acta 2002;337:439–49.10.1016/S0020-1693(02)01113-1Search in Google Scholar

21. Wojciechowska A, Bronowska W, Pietraszko A, Staszak Z, Cieślak-Golonka M. Synthesis, crystal structure and spectroscopic characterisation of double salt [Zn(bpy)3](CrO4)0.5NO36.5H2O. J Mol Struct 2002;608:151–60.10.1016/S0022-2860(01)00924-3Search in Google Scholar

22. Kani I, Kurtca M. Synthesis, characterization, and luminescence of zinc(II) and cadmium(II) coordination complexes: [Zn(phen)2(CH3COO)](ClO4),[Zn(bpy)2(ClO4)](ClO4), and [Cd(phen)2(NO3)2]. Turk J Chem 2013;37: 993–1006.10.3906/kim-1303-39Search in Google Scholar

23. Lan YQ, Li SL, Shao KZ, Wang XL, Du DY, Su Z, et al. A (3,12)-connected 3D metal-organic framework based on nanosized octanuclear zinc clusters. Cryst Growth Des 2008;8:3490–2.10.1021/cg800169nSearch in Google Scholar

24. Nakamoto K. Infrared and Raman spectra of inorganic and coordination compounds, 4th ed. New York: Wiley, 1986:272–80.Search in Google Scholar

25. Opalade AA, Karmakar A, Rúbio GM, Pombeiro AJ, Gerasimchuk N. Zinc complexes with cyanoxime: structural, spectroscopic, and catalysis studies in the pivaloylcyanoxime–Zn system. Inorg chem 2017;56:13962–74.10.1021/acs.inorgchem.7b01891Search in Google Scholar PubMed

26. D’Auria I, Lamberti M, Mazzeo M, Milione S, Roviello G, Pellecchia C. Coordination chemistry and reactivity of zinc complexes supported by a phosphido pincer ligand. Chem Eur J 2012;18:2349–60.10.1002/chem.201102414Search in Google Scholar PubMed

27. Wooten A, Carroll PJ, Maestri AG, Walsh PJ. Unprecedented alkene complex of zinc(II): structures and bonding of divinylzinc complexes. J Am Chem Soc 2006;128:4624–31.10.1021/ja058700xSearch in Google Scholar PubMed PubMed Central

28. Hossain MA, Alam MA, Zahan R, Sheikh CM, Islam MA. Synthesis and characterization of some mixed ligand complexes of Zn(II) with 4,4-bipyridine: anti-inflammatory and analgesic activities of these complexes. Int J Sci Res 2014;6:309–18.10.3329/jsr.v6i2.16994Search in Google Scholar

29. Liu X, Du P, Cao R. Trinuclear zinc complexes for biologically relevant μ 3-oxoanion binding and carbon dioxide fixation. Nat Commun 2013;4:2375.10.1038/ncomms3375Search in Google Scholar PubMed

Received: 2019-01-16
Accepted: 2019-05-24
Published Online: 2019-07-19
Published in Print: 2019-12-18

©2019 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Mitochondrial dysfunction and energy deprivation in the mechanism of neurodegeneration
  4. Research Articles
  5. Cancer diagnosis via fiber optic reflectance spectroscopy system: a meta-analysis study
  6. Development of molecularly imprinted Acrylamide-Acrylamido phenylboronic acid copolymer microbeads for selective glycosaminoglycan separation in children urine
  7. Assessment of LXRα agonist activity and selective antiproliferative efficacy: a study on different parts of Digitalis species
  8. Computational assessment of SKA1 as a potential cancer biomarker
  9. In vitro apoptotic effect of Zinc(II) complex with N-donor heterocyclic ligand on breast cancer cells
  10. A single-tube multiplex qPCR assay for mitochondrial DNA (mtDNA) copy number assessment
  11. A case–control study on effects of the ATM, RAD51 and TP73 genetic variants on colorectal cancer risk
  12. Effects of α-lactalbumin and sulindac on primary and metastatic human colon cancer cell lines
  13. The role of interleukin-9 and interleukin-17 in myocarditis with different etiologies
  14. Gene silencing of Col1α1 by RNAi in rat myocardium fibroblasts
  15. A method for high-purity isolation of neutrophil granulocytes for functional cell migration assays
  16. Role of SNPs of CPTIA and CROT genes in the carnitine-shuttle in coronary artery disease: a case-control study
  17. Interleukin-6 signaling pathway involved in major depressive disorder: selective serotonin reuptake inhibitor regulates IL-6 pathway
  18. Simultaneous comparison of L-NAME and melatonin effects on RAW 264.7 cell line’s iNOS production and activity
  19. Data-mining approach for screening of rare genetic elements associated with predisposition of prostate cancer in South-Asian populations
https://doi.org/10.1515/tjb-2019-0013
Keywords for this article
Metal complex; Zinc; 2,2′-Bipyridine; Breast cancer; Apoptosis

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Mitochondrial dysfunction and energy deprivation in the mechanism of neurodegeneration
  4. Research Articles
  5. Cancer diagnosis via fiber optic reflectance spectroscopy system: a meta-analysis study
  6. Development of molecularly imprinted Acrylamide-Acrylamido phenylboronic acid copolymer microbeads for selective glycosaminoglycan separation in children urine
  7. Assessment of LXRα agonist activity and selective antiproliferative efficacy: a study on different parts of Digitalis species
  8. Computational assessment of SKA1 as a potential cancer biomarker
  9. In vitro apoptotic effect of Zinc(II) complex with N-donor heterocyclic ligand on breast cancer cells
  10. A single-tube multiplex qPCR assay for mitochondrial DNA (mtDNA) copy number assessment
  11. A case–control study on effects of the ATM, RAD51 and TP73 genetic variants on colorectal cancer risk
  12. Effects of α-lactalbumin and sulindac on primary and metastatic human colon cancer cell lines
  13. The role of interleukin-9 and interleukin-17 in myocarditis with different etiologies
  14. Gene silencing of Col1α1 by RNAi in rat myocardium fibroblasts
  15. A method for high-purity isolation of neutrophil granulocytes for functional cell migration assays
  16. Role of SNPs of CPTIA and CROT genes in the carnitine-shuttle in coronary artery disease: a case-control study
  17. Interleukin-6 signaling pathway involved in major depressive disorder: selective serotonin reuptake inhibitor regulates IL-6 pathway
  18. Simultaneous comparison of L-NAME and melatonin effects on RAW 264.7 cell line’s iNOS production and activity
  19. Data-mining approach for screening of rare genetic elements associated with predisposition of prostate cancer in South-Asian populations
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