A novel γ-lactam-based histone deacetylase inhibitor potently inhibits the growth of human breast and renal cancer cells

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Title
A novel γ-lactam-based histone deacetylase inhibitor potently inhibits the growth of human breast and renal cancer cells
Author(s)
H K Kwon; S H Ahn; S H Park; J H Park; J W Park; Hwan Mook Kim; Song Kyu Park; Kiho Lee; Chag Woo Lee; E Choi; G Han; J W Han
Bibliographic Citation
Biological & Pharmaceutical Bulletin, vol. 32, no. 10, pp. 1723-1727
Publication Year
2009
Abstract
We evaluated the novel γ-lactam-based analogue, KBH-A145, for its anticancer activities. KBH-A145 markedly inhibited histone deacetylase (HDAC) activity in vitro and in vivo to an extent comparable to suberoylanilide hydroxamic acid (SAHA). The proliferation of various types of cancers was significantly suppressed by KBH-A145, among which MDA-MB-231 and MCF, human breast cancer cells and ACHN human renal cancer cells, were most sensitive. This was accompanied by induction of p21WAF1/Cip1 through compromised recruitment of HDAC1, which leads to hyperacetylation of its promoter region and thus arrested both cells in the G2/M phase. Interestingly, this compound induced apoptosis of MDA-MB-231 cells, but not ACHN cells, through cleavage of poly(ADP-ribose) polymerase (PARP). Taken together, these results show that this novel γ-lactam-based HDAC inhibitor potently inhibits the growth of human breast and renal cancer cells. Thus KBH-A145 is a potential therapeutic agent for the treatment of these types of cancer.
Keyword
γ-lactam hydroxamic acidAntiproliferationApoptosisHistone deacetylasep21WAF1/Cip1
ISSN
0918-6158
Publisher
Pharmaceutical Soc Japan
DOI
http://dx.doi.org/10.1248/bpb.32.1723
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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