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Histone deacetylase inhibitor trichostatin a induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells

✍ Scribed by Yo-ichi Yamashita; Mitsuo Shimada; Norifumi Harimoto; Tatsuya Rikimaru; Ken Shirabe; Shinj Tanaka; Keizo Sugimachi

Publisher
John Wiley and Sons
Year
2002
Tongue
French
Weight
212 KB
Volume
103
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh‐7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh‐7. It inhibited cell proliferation in vitro and induced G~0~/G~1~ arrest in HepG2 and apoptosis in Huh‐7. Gene expression of liver‐specific functions and liver‐enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh‐7. Our results indicate that TSA can induce cell‐cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines. © 2002 Wiley‐Liss, Inc.

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