SIRT1 Suppresses Breast Cancer Growth Through Downregulation of the Bcl-2 Protein

Oncol Rep. 2013 Jul;30(1):125-30. doi: 10.3892/or.2013.2470. Epub 2013 May 15.

Abstract

Silent mating-type information regulation 2 homologue 1 (SIRT1), a member of the class III histone deacetylase (HDAC) family, is the mammalian ortholog of yeast Sir2. It has been reported to play a key role in a variety of physiological processes such as genomic stability, metabolism, neurogenesis and cell survival. The deacetylase function of SIRT1 has been suggested to play a role in prolonging the life of mammals. However, the suggested functions of SIRT1 as a potential tumor promoter have been challenged by observations of their respective downregulation and upregulation in various types of cancer. Breast cancer patients were included in the present study between 2007 and 2008. Their tumor tissues and paired normal breast tissues were collected and used for evaluation of the expression levels of SIRT1 and Ki67. The effects of SIRT1 on human breast cancer cell lines were also investigated. Immunohistochemistry showed that there is a high correlation between SIRT1 and Ki67 expression. Following treatment with sirtinol (inhibitor of SIRT1), the expression of the pro-survival protein Bcl-2 was markedly decreased in both MCF-7 and MDA-MB-231 cell lines, particularly in MDA-MB-231. Results of the present study revealed that inhibition of SIRT1 activity may be a promising chemotherapeutic strategy against breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / pharmacology
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ki-67 Antigen / metabolism*
  • MCF-7 Cells
  • Naphthols / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / metabolism*

Substances

  • Benzamides
  • Ki-67 Antigen
  • Naphthols
  • Proto-Oncogene Proteins c-bcl-2
  • sirtinol
  • SIRT1 protein, human
  • Sirtuin 1