The p53 induced Siva-1 plays a significant role in cisplatin-induced apoptosis

John L. Barkinge*, Radhika Gudi, Hawkins Sarah, Fei Chu, Alip Borthakur, Bellur S. Prabhakar, Kanteti V.S. Prasad

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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 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.

Original languageEnglish (US)
Article number2
JournalJournal of Carcinogenesis
Volume8
DOIs
StatePublished - Feb 7 2009

Keywords

  • Apoptosis
  • Bcl-2 family
  • Cisplatin
  • Cytochrome c
  • Siva-1
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Health, Toxicology and Mutagenesis

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