Snake venom toxin inhibits cell growth through induction of apoptosis in neuroblastoma cells.
Snake venom toxin from Vipera lebetina turanica can induce apoptosis in many cancer cell lines, but there is no study about the apoptotic effect of snake venom toxin on human neuroblastoma cells. In this study, we investigated the apoptotic effect of snake venom toxin in human neuroblastoma SK-N-MC and SK-N-SH cells. Our result showed that cell detachment and apoptotic cell death were increased by snake venom toxin (1.25-10 microg/mL), but normal neuronal cells were not affected. Consistent with the induction of apoptosis, the level of reactive oxygen species (ROS) was increased, but mitochondrial membrane potential (MMP) was disrupted by treatment with snake venom toxin. However, the glutathione prevented snake venom toxin-induced cell growth inhibition. Snake venom toxin also increased the expression of pro-apoptotic protein Bax, but down-regulated anti-apoptotic protein Bcl-2. Therefore, these results showed that snake venom toxin from Vipera lebetina turanica causes apoptotic cell death of neuroblastoma cells through ROS dependent MMP disruption, and suggested that snake venom toxin may be applicable as an anti-cancer agent for neuroblastoma.
Park
Mi Hee
MH
College of Pharmacy and CBITRC, Chungbuk National University, Cheongju 361-763, Korea.
Son
Dong Ju
DJ
Kwak
Dong Hoon
DH
Song
Ho Sueb
HS
Oh
Ki-Wan
KW
Yoo
Hwan-Soo
HS
Lee
Yong Moon
YM
Song
Min Jong
MJ
Hong
Jin Tae
JT
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014757:Viper Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D017819:Viperidae; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014757:Viper Venoms; D051028:bcl-2-Associated X Protein