Antitumor activity of SK-7041, a novel histone deacetylase inhibitor, in human lung and breast cancer cells

Anticancer Res. 2006 Sep-Oct;26(5A):3429-38.

Abstract

Background: A class of synthetic histone deacetylase (HDAC) inhibitors, which are hybrids of trichostatin A and MS-275 were previously developed. In this study, the antitumor effects of SK-7041, one of those novel HDAC inhibitors, was evaluated on lung and breast cancer cell lines.

Materials and methods: Human lung and breast cancer cells, as well as normal human bronchial epithelial (NHBE) cells were treated with SK-7041, and results were compared with those of cells treated with suberoylanilide hydroxamic acid (SAHA).

Results: SK-7041 induced time-dependent histone hyperacetylation and showed more potent cytotoxicity than SAHA in cancer cells. These antiproliferative effects of SK-7041 were due to apoptotic cell death caused by G2/M-phase arrest and to a lesser extent to G1 arrest. Moreover, SK-7041 inhibited cancer cell proliferation more selectively than NHBE cell proliferation.

Conclusions: These results suggest that SK-7041 may have potential anticancer activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amides / toxicity*
  • Annexin A5 / metabolism
  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects
  • Biphenyl Compounds / toxicity*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / toxicity*
  • Histone Deacetylase Inhibitors*
  • Humans
  • Hydroxamic Acids / toxicity
  • Immunoblotting
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Vorinostat

Substances

  • Amides
  • Annexin A5
  • Antineoplastic Agents
  • Biphenyl Compounds
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • SK-7041
  • Vorinostat