Cytotoxic effects of suramin against HepG2 cells through activation of intrinsic apoptotic pathway

作者: Mohammed M. Al-Gayyar , Mohammed M. Al-Gayyar , Amal M. El-Gayar , Mohamed A. Ebrahim , Ahmed Salah Ibrahim

DOI:

关键词:

摘要: PURPOSE To investigate the cytotoxic activity of suramin against HepG2 human HCC cell line. METHODS cells were treated with 15, 30 and 45 μM suramin. proliferation was measured by MTT lactate dehydrogenase (LDH) assays. Heparan sulfate proteoglycans (HSPGs), glucuronic acid glucosamine levels measured. Moreover, apoptosis assessed measuring caspase-8 caspase-9 activities. The effect on compared same doses a standard drug, cisplatin. RESULTS Suramin blocked heparanase leading to dose-dependent increase in HSPGs reduction levels. reduced survival showed cytotoxicity manner LD50 45.04 μM, cisplatin (LD50 28.9 μM) (p<0.05). able but not caspase-8. CONCLUSION possesses properties, which can be partially explained its ability inhibit restore HSPGs. activates intrinsic without affecting extrinsic pathway.

参考文章(32)
Xiao-mei Han, Jian-min Yang, Han Gao, Yong-lie Zhou, Hou-quan Tao, Hui-ju Wang, Zai-yuan Ye, [Effects of anti-heparanase antibody on the growth and invasion of HCCLM6 human hepatocellular carcinoma cells]. Chinese journal of oncology. ,vol. 31, pp. 10- 14 ,(2009) , 10.3760/CMA.J.ISSN.0253-3766.2009.01.003
Xia Wang, Yan-Yan Yan, Jia-Li Zhao, Yan Guo, Cun-Gen Ma, Chen Wang, Wei Zhang, Triterpenoid pristimerin induced HepG2 cells apoptosis through ROS-mediated mitochondrial dysfunction. Journal of B.U.ON. : official journal of the Balkan Union of Oncology. ,vol. 18, pp. 477- 485 ,(2013)
Israel Vlodavsky, Yael Friedmann, Michael Elkin, Helena Aingorn, Ruth Atzmon, Rivka Ishai-Michaeli, Menachem Bitan, Orit Pappo, Tuvia Peretz, Israel Michal, Larissa Spector, Iris Pecker, Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nature Medicine. ,vol. 5, pp. 793- 802 ,(1999) , 10.1038/10518
Mohamed M. Darweish, Ahmed Abbas, Mohamed A. Ebrahim, Mohammed M.H. Al-Gayyar, Chemopreventive and hepatoprotective effects of Epigallocatechin-gallate against hepatocellular carcinoma: role of heparan sulfate proteoglycans pathway. Journal of Pharmacy and Pharmacology. ,vol. 66, pp. 1032- 1045 ,(2014) , 10.1111/JPHP.12229
Leslie Alderman Elson, Walter Thomas James Morgan, A colorimetric method for the determination of glucosamine and chondrosamine Biochemical Journal. ,vol. 27, pp. 1824- 1828 ,(1933) , 10.1042/BJ0271824
Lawrence R. Dechatelet, Charles E. McCall, Linda C. McPhail, Richard B. Johnston, Superoxide Dismutase Activity in Leukocytes Journal of Clinical Investigation. ,vol. 53, pp. 1197- 1201 ,(1974) , 10.1172/JCI107659
Gil Arvatz, Itay Shafat, Flonia Levy-Adam, Neta Ilan, Israel Vlodavsky, The heparanase system and tumor metastasis: is heparanase the seed and soil? Cancer and Metastasis Reviews. ,vol. 30, pp. 253- 268 ,(2011) , 10.1007/S10555-011-9288-X
Ahmed Tayel, Khaled H. Abd El Galil, Mohamed A. Ebrahim, Ahmed S. Ibrahim, Amal M. El-Gayar, Mohammed M.H. Al-Gayyar, Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme European Journal of Pharmacology. ,vol. 728, pp. 151- 160 ,(2014) , 10.1016/J.EJPHAR.2014.02.001