Snake venom toxin from vipera lebetina turanicainduces apoptosis of colon cancer cells via upregulation of ROS- and JNK-mediated death receptor expression

BMC Cancer

Research Article

MiRan Jo¹  Dohee Won¹  Mi Hee Park¹ 

[1] College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, 361-763, Cheongju, Chungbuk, South Korea;

关键词: Snake venom toxin;    Apoptosis;    Death receptor;    ROS;    JNK;   

DOI  :  10.1186/1471-2407-12-228

 received in 2012-02-01, accepted in 2012-05-16,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAbundant research suggested that the cancer cells avoid destruction by the immune system through down-regulation or mutation of death receptors. Therefore, it is very important that finding the agents that increase the death receptors of cancer cells. In this study, we demonstrated that the snake venom toxin from Vipera lebetina turanica induce the apoptosis of colon cancer cells through reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) dependent death receptor (DR4 and DR5) expression.MethodsWe used cell viability assays, DAPI/TUNEL assays, as well as western blot for detection of apoptosis related proteins and DRs to demonstrate that snake venom toxin-induced apoptosis is DR4 and DR5 dependent. We carried out transient siRNA knockdowns of DR4 and DR5 in colon cancer cells.ResultsWe showed that snake venom toxin inhibited growth of colon cancer cells through induction of apoptosis. We also showed that the expression of DR4 and DR5 was increased by treatment of snake venom toxin. Moreover, knockdown of DR4 or DR5 reversed the effect of snake venom toxin. Snake venom toxin also induced JNK phosphorylation and ROS generation, however, pretreatment of JNK inhibitor and ROS scavenger reversed the inhibitory effect of snake venom toxin on cancer cell proliferation, and reduced the snake venom toxin-induced upregulation of DR4 and DR5 expression.ConclusionsOur results indicated that snake venom toxin could inhibit human colon cancer cell growth, and these effects may be related to ROS and JNK mediated activation of death receptor (DR4 and DR5) signals.

【 授权许可】

Unknown   
© Park et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.