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

Background Abundant 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 t...

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Bibliographic Details
Published inBMC cancer Vol. 12; no. 1
Main Authors Park, Mi Hee, Jo, MiRan, Won, Dohee, Song, Ho Sueb, Han, Sang Bae, Song, Min Jong, Hong, Jin Tae
Format Journal Article
LanguageEnglish
Published BioMed Central Ltd 08.06.2012
Subjects
Apoptosis
Cancer
Cancer cells
Care and treatment
Colon cancer
Development and progression
Genetic aspects
Health aspects
Physiological aspects
Poisonous snakes
Proteins
Venom
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Summary:Background Abundant 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. Methods We 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. Results We 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. Conclusions Our 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. Keywords: Snake venom toxin, Apoptosis, Death receptor, ROS, JNK
ISSN:1471-2407
1471-2407
DOI:10.1186/1471-2407-12-228