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Title 

A novel delta-lactam-based histone deacetylase inhibitor, KBH-A42, induces cell cycle arrest and apoptosis in colon cancer cells

Authors 

Moo Rim KangJong Soon KangS B HanJang Hyun KimD M KimKiho LeeChang Woo LeeKi Hoon LeeC H LeeG HanJ S KangHwan Mook KimSong Kyu Park

Publisher 

Elsevier

Issue Date 

2009

Citation 

Biochemical Pharmacology, vol. 78, no. 5, pp. 486-494

Keywords 

HDACKBH-A42colon cancercell cycle arrestapoptosis

Abstract 

In this study, we investigated the anti-tumor activity of KBH-A42 [N-hydroxy-3-(2-oxo-1-(3-phenylpropyl)-1,2,5,6-tetrahydropyridin-3-yl)propanamide], a novel synthetic histone deacetylase (HDAC) inhibitor. KBH-A42 inhibited a variety of HDAC isoforms in enzyme assays and suppressed growth of various cancer cell lines. Among the cell lines examined, colon cancer cells, including SW620, SW480 and HCT-15, were the cell types most sensitive to KBH-A42. KBH-A42 inhibition of cancer cell growth was comparable to or stronger than that of suberoylanilide hydroxamic acid (SAHA), a wellknown HDAC inhibitor approved by the FDA to treat cutaneous T cell lymphomas. In SW620 cells, KBHA42 increased the acetylation of histones, mediated cell cycle arrest (G1 arrest at low doses and G2 arrest at high doses), and induced apoptosis. The cell cycle arrest and apoptosis induced by KBH-A42 might be mediated through up-regulation of p21Waf1 and activation of caspases, respectively. In addition, KBHA42 inhibited SW620 tumor growth in a human tumor xenograft model. Taken together, our results indicate that KBH-A42 exerts an anti-tumor activity in vitro and in vivo and is a promising therapeutic candidate to treat human cancers.

ISSN 

0006-2952

Link 

http://dx.doi.org/10.1016/j.bcp.2009.05.010

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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