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

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.

• Authors: Eun-Ryeong Hahm, Shivendra V Singh
• Journal: Cancer letters (Cancer Lett) Vol. 334 Issue 1 Pg. 101-8 (Jun 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22935676 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

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