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

BMC Cancer

Mi Hee Park²  MiRan Jo²  Dohee Won²  Ho Sueb Song³  Sang Bae Han²  Min Jong Song¹  Jin Tae Hong¹ 

[1] College of Pharmacy and Medical Research Center, Chungbuk National University, 48 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea

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

[3] College of Oriental Medicine, Kyungwon University, San 65 Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii

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

Others  :  1080379
DOI  :  10.1186/1471-2407-12-228

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

【 摘 要 】

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.

【 授权许可】

   
2012 Park et al; licensee BioMed Central Ltd.

【 图 表 】

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