Gambogic acid reduced bcl-2 expression via p53 in human breast MCF-7 cancer cells

J Cancer Res Clin Oncol. 2009 Dec;135(12):1777-82. doi: 10.1007/s00432-009-0624-2. Epub 2009 Jul 7.

Abstract

Purpose: In this study, we investigated the correlation between p53 and bcl-2 in gambogic acid (GA)-induced apoptosis.

Method: MTT assay was employed to evaluate MCF-7 cell viability after GA treatment. Cell morphological changes were observed follow-up under the inverted microscope after GA withdrawal. To observe the cell apoptosis, DAPI staining was used. Meanwhile, p53 small interfering RNA (si-RNA) was adopted to knock p53 down. All expressions of p53 and bcl-2 were evaluated by Western blot analysis.

Results: MTT assay showed that GA inhibited MCF-7 cell growth effectively in a time-dependent manner. With 0.5 h GA treatment, p53 was significantly increased, whereas bcl-2 was reduced potently with 6 h GA treatment. After GA withdrawal, p53 expressions were maintained in high levels. Furthermore, bcl-2 decreasing was attenuated after co-treatment with PFT alpha, a p53 transcription blocker. Same result was observed after p53 knock-down by p53 si-RNA.

Conclusions: Gambogic acid induced human breast cancer cells MCF-7 apoptosis by reducing bcl-2 expression via p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor*
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Models, Biological
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Small Interfering / pharmacology
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / physiology*
  • Xanthones / pharmacology*

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Xanthones
  • gambogic acid