Identification of a p53-dependent pathway in the induction of apoptosis of human breast cancer cells by the natural product, resveratrol

J Altern Complement Med. 2004 Apr;10(2):235-9. doi: 10.1089/107555304323062211.

Abstract

Objective: Resveratrol, a constituent found in grapes and various other plants, has been shown to have chemo-preventive activity against cancer, and specifically demonstrated to induce apoptosis by p53-dependent pathways in murine cells. The goal of this research was to identify the role of p53-dependent or p53-independent pathways in the induction of apoptosis in human breast cancer cells by this natural product.

Design: A number of human breast cancer cell lines, as well as a control of a wild-type line (astrocytoma N 1321N1), were investigated for induction of apoptosis by resveratrol using both microscopic evaluation and DNA fragmentation assays. Concurrently, we established the p53 gene status (wild-type or mutant) of each cell line by Western blot using p53-specific antibody.

Results: Apoptosis induced by resveratrol was found to occur only in breast cancer cells expressing wild-type p53 but not in mutant p53-expressing cells.

Conclusions: We therefore conclude that the natural product, resveratrol, induces apoptosis in breast cancer cells via p53-dependent pathways.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Astrocytoma / drug therapy
  • Astrocytoma / metabolism
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Transformation, Neoplastic / drug effects*
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Time Factors
  • Transcriptional Activation / drug effects
  • Tumor Suppressor Protein p53 / drug effects*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Stilbenes
  • Tumor Suppressor Protein p53
  • Resveratrol