We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The p53 induced Siva-1 plays a signifi cant role in cisplatin-induced apoptosis.
- Authors
Barkinge, John L.; Gudi, Radhika; Sarah, Hawkins; Chu, Fei; Borthakur, Alip; Prabhakar, Bellur S.; Prasad, Kanteti V. S.
- Abstract
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 specifi cally 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 signifi cant 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 signifi cant role in DNA damage-induced cell death.
- Subjects
CISPLATIN; APOPTOSIS; DRUG therapy; OLIGOMERIZATION; CANCER cells
- Publication
Journal of Carcinogenesis, 2009, Vol 8, Issue 1, p1
- ISSN
0974-6773
- Publication type
Article
- DOI
10.4103/1477-3163.45389