The growth inhibitory effects of garlic polysaccharide combined with cis-dichlorodiamine platinum on human HepG2 cells

Liyan Li; Tao Huang; Chong Lan; An Jia; Yang Mao

doi:10.1515/biolog-2017-0155

Article

The growth inhibitory effects of garlic polysaccharide combined with cis-dichlorodiamine platinum on human HepG2 cells

Liyan Li , Tao Huang , Chong Lan , An Jia and Yang Mao

Published/Copyright: December 29, 2017

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From the journal Biologia Volume 72 Issue 11

Abstract

The growth inhibitory effects of garlic polysaccharide (GPS) combined with cis-dichlorodiamine platinum (DDP) on human HepG2 cells were evaluated in this paper. Our results showed that GPS, with a molecular weight of 2,714.94 Da, was isolated by precipitation and purification, and composed of glucose, galactose, xylose and arabinose with a relative molar ratio of 4.6: 0.8: 0.9: 0.5. GPS inhibited the proliferation of HepG2 cells. While, compared with GPS and DDP treated alone, the combination agents enhanced significantly growth inhibitory effect on HepG2 cells in a time- and dose-dependent manner. Propidium iodide/annexin V staining analyzed by flow cytometry demonstrated that GPS enhanced the cytotoxic effects of chemotherapeutic drug DDP on tumor cells. Cell cycle arrest of HepG2 treated with the combined compounds occurred in S/G2 phase. Western blot analysis revealed that the GPS can up-regulate the pro-apoptotic protein Bax. Our research provides additional evidence to develop combination therapies of GPS and DDP for human hepatic tumor and a potential way to decrease the side effect of DDP by combining GPS treatment.

Key words: garlic polysaccharide; DDP; human HepG2 cells; growth inhibitory effect

Acknowledgements

This work was supported by Science and Technology Bureau of Zhengzhou City (Grant No. 141PPTGG402) and Henan Provincial Department of Education (Grant No. 15A350008).

References

Badvie S. 2000. Hepatocellular carcinoma. Postgrad. Med. J. 76: 4–11.10.1136/pmj.76.891.4Search in Google Scholar PubMed

Barabas K., Milner R., Lurie D. & Adin C. 2008. Cisplatin: a review of toxicities and therapeutic applications. Vet. Comp. Oncol. 6: 1–18.10.1111/j.1476-5829.2007.00142.xSearch in Google Scholar PubMed

Bosch F.X., Ribes J. & Borras J.1999. Epidemiology of primary liver cancer. Semin. Liver Dis. 19: 271–285.10.1055/s-2007-1007117Search in Google Scholar PubMed

Büttner N., Schmidt N. & Thimme R. 2016. Perspectives of immunotherapy in hepatocellular carcinoma (HCC). Bibliography 54: 1334–1342.10.1055/s-0042-120417Search in Google Scholar

Chandrashekar P.M., Prashanth K.V. & Venkatesh Y.P. 2011. Isolation, structural elucidation and immunomodulatory activity of fructans from aged garlic extract. Phytochemistry 72: 255–264.10.1016/j.phytochem.2010.11.015Search in Google Scholar PubMed

Chena J.L., Cheonga K.L., Song Z.L., Shi Y.J. & Huang X.S. 2013. Structure and protective effect on UVB-induced keratinocyte damage of fructan from white garlic. Carbohydr. Polym. 92: 200–205.10.1016/j.carbpol.2012.09.068Search in Google Scholar PubMed

Chu G. 1994. Cellular responses to cisplatin: the roles of DNA-binding proteins and DNA repair. J. Biol. Chem. 269: 787–790.10.1016/S0021-9258(17)42175-2Search in Google Scholar PubMed

Cui H.Y., Wu S.F., Sun Y.P., Wang T.T., Li Z.J., Chen M.H. & Wang C.L. 2016. Polysaccharide from Pleurotus nebrodensis induces apoptosis via mitochondrial pathway in HepG2 cells. Food Funct. 7: 455–463.10.1039/C5FO00884KSearch in Google Scholar PubMed

Farazi P.A., Glickman J, Horner J. & Depinho R.A. 2006. Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression. Cancer Res. 66: 4766–4773.10.1158/0008-5472.CAN-05-4608Search in Google Scholar PubMed

Hall M.D., Okabe M., Shen D.W., Liang X.J. & Gottesman M.M. 2008. The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy. Annu. Rev. Pharmacol. Toxicol. 48: 495–535.10.1146/annurev.pharmtox.48.080907.180426Search in Google Scholar PubMed

Hata A.N., Engelman J.A. & Faber A.C. 2015. The Bcl2 Family: key mediators of the apoptotic response to targeted anticancer therapeutics. Cancer Discov. 5: 475–487.10.1158/2159-8290.CD-15-0011Search in Google Scholar PubMed

Honda S., Suzuki S., Kakehi K., Honda A. & Takai T. 1981. Analysis of the monosaccharide compositions of total non-dialyzable urinary glycol-conjugates by the dithioacetal method. J. Chromatogr. 226: 341–350.10.1016/S0378-4347(00)86068-5Search in Google Scholar

Lehnert M. 1994. Multidrug resistance in human cancer. J. Neurooncol. 22: 239–243.10.1007/BF01052927Search in Google Scholar PubMed

Li L.Y. & Huang T. 2017. Growth inhibitory effects of garlic polysaccharide on human HepG2 cells. Agric. Sci. Technol. 18: 988–992.Search in Google Scholar

Li S.H., Gao A., Dong S., Chen Y., Sun S., Lei Z.F. & Zhang Z.Y. 2017. Purification, antitumor and immunomodulatory activity of polysaccharides from soybean residue fermented with Morchella esculenta. Int. J. Biol. Macromol. 96: 26–34.10.1016/j.ijbiomac.2016.12.007Search in Google Scholar

Liu J.C., Zhang C.J., Wang Y.J., Yu H.T., Liu H., Wang L.P., Yang X.Z., Liu Z.C., Wen X.C., Sun YX., Yu C.L. & Liu L. 2011. Structural elucidation of a heteroglycan from the fruiting bodies of Agaricus blazei Murill. Int. J. Biol. Macromol. 49: 716–720.10.1016/j.ijbiomac.2011.07.003Search in Google Scholar PubMed

Lu X.M., Li N.Y., Qiao X.G., Qiu Z.C. & Liu P.L. 2017. Composition analysis and antioxidant properties of black garlic extract. J. Food Drug Anal. 25: 340–349.10.1016/j.jfda.2016.05.011Search in Google Scholar PubMed

Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65: 55–63.10.1016/0022-1759(83)90303-4Search in Google Scholar PubMed

Motola K.D., Zamora V.D., Uribe M. & Mendez S.N. 2006. Hepatocellular carcinoma. An overview. Ann. Hematol. 5: 16–24.10.1016/S1665-2681(19)32034-4Search in Google Scholar

Nagai N. & Ogata H. 1997. Quantitative relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity in rats: importance of area under the concentration time curve (auc) as the major toxicodynamic determinant in vivo. Cancer Chemother. Pharmacol. 40: 11–18.10.1007/s002800050618Search in Google Scholar PubMed

Pan S.K. & Wu S.J. 2014. Cellulase-assisted extraction and antioxidant activity of the polysaccharides from garlic. Carbohydr. Polym. 111: 606–609.10.1016/j.carbpol.2014.05.022Search in Google Scholar PubMed

Pardee A.D. & Butterfield L.H. 2012. Immunotherapy of hepatocellular carcinoma: unique challenges and clinical opportunities. Oncoimmunology 1: 48–55.10.4161/onci.1.1.18344Search in Google Scholar PubMed

Prieto J., Melero I. & Sangro B. 2015. Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat. Rev G.astroenterol. Hepatol. 12: 681–700.10.1038/nrgastro.2015.173Search in Google Scholar

Sabine B., Thomas G.D., Werner P. & Heinz F. 2000. Characterization of the high molecular weight fructan isolated from garlic (Allium sativum L.). Carbohydr. Res. 328: 177–183.10.1016/S0008-6215(00)00097-5Search in Google Scholar

Stewart D.J., Dulberg C.S., Mikhael N.Z., Redmond M.R., Montpetit V.A.J. & Goel R. 1997. Association of cisplatin nephrotoxicity with patient characteristics and cisplatin administration methods. Cancer Chemother. Pharmacol. 40: 293–308.10.1007/s002800050661Search in Google Scholar PubMed

Su J., Jiang L., Wu J., Liu Z. & Wu Y. 2016. Anti-tumor and antivirus activity of polysaccharides extracted from Sipunculus nudus (SNP) on Hepg2.2.15. Int. J. Biol. Macromol. 87: 597– 602.10.1016/j.ijbiomac.2016.03.022Search in Google Scholar PubMed

Tian Y.T., Zhao Y.T., Zeng H.L., Zhang Y.L. & Zheng B.D. 2016. Structural characterization of a novel neutral polysaccharide from Lentinus giganteus and its antitumor activity through inducing apoptosis. Carbohydr. Polym. 154: 231–240.10.1016/j.carbpol.2016.08.059Search in Google Scholar PubMed

Wang G.B., Dong L.L., Zhang Y.Y., Ji Y.Y., Xiang W.H. & Zhao M. 2012. Polysaccharides from Phellinus linteus inhibit cell growth and invasion and induce apoptosis in HepG2 human hepatocellular carcinoma cells. Biologia 67: 247–254.10.2478/s11756-011-0160-9Search in Google Scholar

Wang G.D., Liu C.Y., Liu J., Liu B., Li P., Qin G.Z., Xu Y.H., Chen K., Liu H.X. & Chen K.S. 2016. Exopolysaccharide from Trichoderma pseudokoningii induces the apoptosis of MCF-7 cells through an intrinsic mitochondrial pathway. Carbohydr. Polym. 136: 1065–1073.10.1016/j.carbpol.2015.09.108Search in Google Scholar PubMed

Xiong F., Jiang M., Huang Z.Z., Chen M.J., Chen K.J., Zhou J., Yin L., Tang Y.P., Wang M.Y., Ye L.H., Zhan Z., Duan J.N., Fu H.A. & Zhang X. 2014. A novel herbal formula induces cell cycle arrest and apoptosis in association with suppressing the P13K/AKT pathway in human lung cancer A549 cells. Integr. Cancer Ther. 13: 152–160.10.1177/1534735413503544Search in Google Scholar PubMed

Zgurskaya H.I. & Nikaido H. 2000. Multidrug resistance mechanisms: drug efflux across two membranes. Mol. Microbiol. 37: 219–225.10.1046/j.1365-2958.2000.01926.xSearch in Google Scholar PubMed

Zhang J., Zhang T. & Ti X.Y. 2010. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through a miRNA signaling pathway. Biochem. Biophys. Res. Commun. 399: 1–6.10.1016/j.bbrc.2010.07.013Search in Google Scholar PubMed

Zhu Q.W., Chen J.H., Li Q., Wang T. & Li H.B. 2016. Antitumor activity of polysaccharide from Laminaria japonica on mice bearing H22 liver cancer. Int. J. Biol. Macromol. 92: 156–158.10.1016/j.ijbiomac.2016.06.090Search in Google Scholar PubMed

Abbreviations
BCA: bicinchoninic acid
DDP: cis-dichlorodiamine platinum
FBS: fetal bovine serum
FCM: flow cytometry
GPS: garlic polysaccharide
HCC: hepatocellular carcinoma
HPLC: high-performance liquid chromatography
HRP: horseradish peroxidase
MEM: modified Eagle’s medium
MTT: 3-(4-5-dimethylthiazol-2-11)-2, 5-diphenyl tetrazolium bromide
PBS: phosphate buffer saline
PI: propidium iodide
PVDF: polyvinylidene difluoride
RIPA: radio immunoprecipitation assay
SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Received: 2017-9-4

Accepted: 2017-11-23

Published Online: 2017-12-29

Published in Print: 2017-11-27

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Articles in the same Issue

https://doi.org/10.1515/biolog-2017-0155

Keywords for this article

garlic polysaccharide; DDP; human HepG2 cells; growth inhibitory effect