Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors

Biochem Biophys Res Commun. 2016 Sep 9;478(1):227-233. doi: 10.1016/j.bbrc.2016.07.063. Epub 2016 Jul 15.

Abstract

SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuating AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies.

Keywords: AKT; Apoptosis; Bcl-2; Cancer; HDAC; SRC-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antibiotics, Antineoplastic / administration & dosage*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Depsipeptides / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Gene Silencing
  • Histone Deacetylase Inhibitors / administration & dosage*
  • Humans
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Nuclear Receptor Coactivator 3 / antagonists & inhibitors
  • Nuclear Receptor Coactivator 3 / genetics*
  • Nuclear Receptor Coactivator 3 / metabolism*

Substances

  • Antibiotics, Antineoplastic
  • Depsipeptides
  • Histone Deacetylase Inhibitors
  • romidepsin
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 3