%0 Journal Article
%T The p53-induced Siva-1 plays a significant role in cisplatin-mediated apoptosis
%A Barkinge John
%A Gudi Radhika
%A Sarah Hawkins
%A Chu Fei
%J Journal of Carcinogenesis
%D 2009
%I Medknow Publications
%X Background: The pro-apoptotic protein Siva-1 functions in both extrinsic and intrinsic cell death signaling; however, the exact contribution of the endogenous Siva-1 to DNA damage-induced apoptosis is unclear. Using cisplatin, a chemotherapeutic drug, to induce DNA damage and cell death, we determined the role of Siva-1. Methods: Cisplatin treated HCT116 colorectal carcinoma cells (p53+/+ and -/-) were used in the study. With the help of recombinant lentivirus that can express siSiva (siRNA that specifically targets Siva-1), we also generated Siva-1 knockdown HCT116 cells. Apoptosis was determined by tetramethyl rhodamine methyl ester (TMRM) staining and propidium iodide (PI) staining. Results: Treatment with cisplatin induced Siva-1 expression in a p53 dependent manner. In Siva-1 knockdown p53+/+ HCT116 colorectal carcinoma cells, loss of Siva-1 expression conferred significant resistance to cisplatin-induced apoptosis. Although Siva-1 levels were positively regulated by p53, Siva-1-induced apoptosis did not require p53. Despite the fact that Siva-1 lacks even a minimal BH3 domain, similar to other proapoptotic Bcl2 family members induced by p53, we showed that Siva-1 mediated apoptosis is characterized by Bax oligomerization and cytochrome c leakage from mitochondria. The putative amphipathic helical region in Siva-1 (SAH) appeared to function analogously to a BH3 domain. Conclusion: The p53 induced Siva-1 is one of the effector molecules, which plays a significant role in DNA damage-induced cell death.
%K Apoptosis
%K Bcl-2 family
%K cisplatin
%K cytochrome c
%K p53
%K Siva-1
%U http://www.carcinogenesis.com/article.asp?issn=1477-3163;year=2009;volume=8;issue=1;spage=2;epage=2;aulast=Barkinge