Withaferin A-induced apoptosis in human breast cancer cells is associated with suppression of inhibitor of apoptosis family protein expression

Cancer Lett. 2013 Jun 28;334(1):101-8. doi: 10.1016/j.canlet.2012.08.026. Epub 2012 Aug 27.

Abstract

The present study provides novel insight into the mechanism of apoptosis induction by withaferin A (WA), which is a bioactive constituent of an Ayurvedic medicine plant (Withania somnifera). Exposure of MDA-MB-231 and MCF-7 human breast cancer cells to WA resulted in suppression of XIAP, cIAP-2, and Survivin protein levels. The WA-induced apoptosis was significantly attenuated by ectopic expression of XIAP, Survivin, and cIAP-2 in both cells. However, the WA-mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with suppression of Survivin protein level only. These results indicate important contribution of Survivin suppression in WA-induced apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • MCF-7 Cells / drug effects
  • Mice, Nude
  • Survivin
  • Ubiquitin-Protein Ligases
  • Withanolides / pharmacology*
  • X-Linked Inhibitor of Apoptosis Protein / genetics
  • X-Linked Inhibitor of Apoptosis Protein / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Survivin
  • Withanolides
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • BIRC3 protein, human
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Ubiquitin-Protein Ligases
  • withaferin A