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

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.

• Authors: Keun-Wook Lee, Jee Hyun Kim, Jung-Hyun Park, Hwang-Phill Kim, Sang-Hyun Song, Sang Gyun Kim, Tai Young Kim, Hyun-Soon Jong, Kyung Hae Jung, Seock-Ah Im, Tae-You Kim, Noe Kyeong Kim, Yung-Jue Bang
• Journal: Anticancer research (Anticancer Res) 2006 Sep-Oct Vol. 26 Issue 5A Pg. 3429-38 ISSN: 0250-7005 [Print] Greece
• PMID: 17094463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Acetylation
• Amides (toxicity)
• Annexin A5 (metabolism)
• Antineoplastic Agents (toxicity)
• Apoptosis (drug effects)
• Biphenyl Compounds (toxicity)
• Breast Neoplasms (metabolism, 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, pathology)
• Tumor Cells, Cultured
• Vorinostat