Synergistic efficacy in human ovarian cancer cells by histone deacetylase inhibitor TSA and proteasome inhibitor PS-341

Cancer Invest. 2011 May;29(4):247-52. doi: 10.3109/07357907.2010.496756. Epub 2011 Feb 23.

Abstract

Histone deacetylase inhibitors and proteasome inhibitor are all emerging as new classes of anticancer agents. We chose TSA and PS-341 to identify whether they have a synergistic efficacy on human ovarian cancer cells. After incubated with 500 nM TSA or/and 40 nM PS-341, we found that combined groups resulted in a striking increase of apoptosis and G2/M blocking rates, no matter in A2780, cisplatin-sensitive ovarian cancer cell line OV2008 or its resistant variant C13*. This demonstrated that TSA interacted synergistically with PS-341, which raised the possibility that combined the two drugs may represent a novel strategy in ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Boronic Acids / pharmacology*
  • Bortezomib
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytochromes c / metabolism
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Female
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Protease Inhibitors / pharmacology*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • Pyrazines / pharmacology*
  • RNA Interference
  • Time Factors

Substances

  • Boronic Acids
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Protease Inhibitors
  • Proteasome Inhibitors
  • Pyrazines
  • trichostatin A
  • Bortezomib
  • Cytochromes c
  • Caspases
  • Proteasome Endopeptidase Complex
  • Cisplatin