Scorpion venom induces glioma cell apoptosis in vivo and inhibits glioma tumor growth in vitro.
Malignant gliomas are the main brain tumors notoriously resistant to currently available therapies, since they fail to undergo apoptosis upon anticancer treatment. Recent progress on enhanced studies of ion channels involved in glioma cells shed new light on the investigation of glioma cell growth and proliferation. Here we report BmK scorpion venom, a rich resource of various ion channels blockers/modulators, induces cell death of cultured malignant glioma U251-MG cells in vitro specifically at a dose of 10 mg/ml while shows no effect on human hepatocellular carcinoma cells and Chinese hamster ovary cells. The glioma cell death was then determined as apoptosis using 4,6-diamidino-2-phenylindole staining and fluorescence-activated cell sorting analysis. After incubation with BmK venom for 32 and 40 h, 36.20% and 63.08% of U251-MG cells showed apoptosis. Furthermore, BmK venom could significantly inhibit the tumor growth in vitro, which was assessed using U251-MG tumor xenografts on severe combined immunodeficiency mice. The tumor volume of the BmK venom treated mice is nearly 1/8 of that of control after 21 days, and the tumor weight is less than half of that of control. That BmK venom induces apoptosis and inhibits growth of glioma may result from the inhibition and/or modulation of various ion channels in glioma cells.
Wang
Wei-Xi
WX
Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Ji
Yong-Hua
YH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D016466:CHO Cells; D002277:Carcinoma / Q000188:drug therapy; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D051379:Mice; D016513:Mice, SCID; D012604:Scorpion Venoms / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007473:Ion Channels; D012604:Scorpion Venoms