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

John L Barkinge1, Radhika Gudi, Hawkins Sarah

  • 1Department of Microbiology and Immunology, University of Illinois at Chicago, 835 S. Wolcott Ave., MC 790, Chicago, IL 60612, USA.

Journal of Carcinogenesis
|February 26, 2009
PubMed
Abstract

Insights

The pro-apoptotic protein Siva-1 is induced by DNA damage in a p53-dependent manner. Siva-1 knockdown confers resistance to cisplatin-induced apoptosis, highlighting its role in cell death signaling.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The pro-apoptotic protein Siva-1 is involved in extrinsic and intrinsic cell death pathways.
  • The specific role of endogenous Siva-1 in DNA damage-induced apoptosis remains unclear.

Purpose of the Study:

  • To investigate the role of Siva-1 in DNA damage-induced apoptosis using cisplatin.
  • To elucidate the relationship between p53 and Siva-1 in the apoptotic process.

Main Methods:

  • Utilized HCT116 colorectal carcinoma cells (p53+/+ and p53-/-).
  • Generated Siva-1 knockdown HCT116 cells using lentiviral siRNA (siSiva).
  • Assessed apoptosis via tetramethyl rhodamine methyl ester (TMRM) and propidium iodide (PI) staining.

Main Results:

  • Cisplatin treatment induced Siva-1 expression in a p53-dependent manner.
  • Siva-1 knockdown significantly increased resistance to cisplatin-induced apoptosis in p53+/+ cells.
  • Siva-1-mediated apoptosis involved Bax oligomerization and cytochrome c release, independent of p53, with its putative amphipathic helical region functioning similarly to a BH3 domain.

Conclusions:

  • p53-induced Siva-1 is a key effector molecule in DNA damage-induced cell death.
  • Siva-1 plays a significant role in mediating apoptosis following DNA damage.

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