Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor κB and signal transducer and activator of transcription 3.
Snake venom toxin from Vipera lebetina turanica induces apoptosis in many cancer cell lines, but there is no study about the apoptotic effect of snake venom toxin on human ovarian cancer cells. In this study, we investigated the apoptotic effect of snake venom toxin in human ovarian cancer PA-1 and SK-OV3 cells. Snake venom toxin dose dependently (0∼10 μg/mL) inhibited ovarian cancer cell growth with IC(50) values 4.5 μg/mL in PA-1 cells, and 6.5 μg/mL in SK-OV3 cells. Our results also showed that apoptotic cell death increased by snake venom toxin in a dose dependent manner (0∼10 μg/mL). Consistent with increased cell death, snake venom toxin increased the expression of pro-apoptotic protein Bax and caspase-3, but down-regulated anti-apoptotic protein Bcl-2. Untreated ovarian cancer cells showed a high DNA binding activity of nuclear factor B (NF-κB), but it was inhibited by snake venom toxin accompanied by inhibition of p50 and p65 translocation into the nucleus as well as phosphorylation of inhibitory κB. Snake venom toxin also inhibited DNA binding activity of the signal transducer and activator of transcription 3 (STAT3). Moreover, the combination treatment of NF-κB (salicylic acid, 1 or 5 μM) and STAT3 (stattic, 1 μM) with snake venom toxin (1 μg/mL) further enhanced cell growth inhibitory effects of snake venom toxin. These results showed that snake venom toxin from Vipera lebetina turanica caused apoptotic cell death of ovarian cancer cells through the inhibition of NF-κB and STAT3 signal, and suggested that snake venom toxin may be applicable as an anticancer agent for ovarian cancer.
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea.
Ju Kyoung
JK
Song
Mi Ran
MR
Jo
Mi Hee
MH
Park
Ho Sueb
HS
Song
Byeong Jun
BJ
An
Min Jong
MJ
Song
Sang Bae
SB
Han
Jin Tae
JT
Hong
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014757:Viper Venoms / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use
D006131:Growth Inhibitors; D016328:NF-kappa B; D009498:Neurotoxins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014757:Viper Venoms