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

Hyoung Keun Kwon, Seong Hoon Ahn, Se Hong Park, Jae Hyun Park, Jong Woo Park, Hwan Mook Kim, Song Kyu Park, Kiho Lee, Chang Woo Lee, Eunhyun Choi, Gyoonhee Han, Jeung Whan Han

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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.

Original languageEnglish
Pages (from-to)1723-1727
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume32
Issue number10
DOIs
Publication statusPublished - 2009 Oct 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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    Kwon, H. K., Ahn, S. H., Park, S. H., Park, J. H., Park, J. W., Kim, H. M., Park, S. K., Lee, K., Lee, C. W., Choi, E., Han, G., & Han, J. W. (2009). A novel γ-lactam-based histone deacetylase inhibitor potently inhibits the growth of human breast and renal cancer cells. Biological and Pharmaceutical Bulletin, 32(10), 1723-1727. https://doi.org/10.1248/bpb.32.1723