Antitumor effects of a novel sulfur-containing hydroxamate histone deacetylase inhibitor H40
✍ Scribed by Juan Long; Jinyan Zhao; Zheng Yan; Ziliang Liu; Nan Wang
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- French
- Weight
- 468 KB
- Volume
- 124
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Histone deacetylase (HDAC) inhibitors are among the most promising targeted anticancer agents and are potent inducers of growth arrest, differentiation, and/or apoptotic cell death of transformed cells. In this study, antitumor effects of a novel sulfur‐containing hydroxamate HDAC inhibitor, H40, were observed and compared with a typical HDAC inhibitor SAHA. In biochemical HDAC assay, H40 showed a potent HDAC inhibition. It induced histone H3 hyperacetylation, correlating with inhibition of cancer cell proliferation, induction of cell differentiation and cell cycle blockage. A broad cytotoxicity was observed across cell lines from different tumor entities. The autophagy rather than apoptosis inducing activity for both H40 and SAHA was observed in prostate cancer PC‐3M cells. HDAC inhibitor‐induced p21^CIP/WAF1^ expression was evident in PC‐3M and HL‐60 cell lines. The in vivo efficacy of H40 against a murine prostate carcinoma TRAMP‐C2 was compared with that of SAHA, which showed that H40 exerted a favorable antitumor action when only administered twice a week. We conclude that H40 might have clinical value in cancer chemotherapy and warrants further investigation in this regard. © 2008 Wiley‐Liss, Inc.
📜 SIMILAR VOLUMES