Gene expression profiling of KBH-A42, a novel histone deacetylase inhibitor, in human leukemia and bladder cancer cell lines

Kang,Moo Rim; Kang,Jong Soon; Yang,Jeong Wook; Kim,Bo Geun; Kim,Jin‑Ah; Jo,Yeong Nang; Lee,Kiho; Lee,Chang Woo; Lee,Ki Hoon; Yun,Jieun; Kim,Hwan Mook; Han,Gyoonhee; Kang,Jong Seong; Park,Song-Kyu

doi:10.3892/ol.2011.430

Gene expression profiling of KBH-A42, a novel histone deacetylase inhibitor, in human leukemia and bladder cancer cell lines

Authors:
- Moo Rim Kang
- Jong Soon Kang
- Jeong Wook Yang
- Bo Geun Kim
- Jin‑Ah Kim
- Yeong Nang Jo
- Kiho Lee
- Chang Woo Lee
- Ki Hoon Lee
- Jieun Yun
- Hwan Mook Kim
- Gyoonhee Han
- Jong Seong Kang
- Song-Kyu Park
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Affiliations: Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk 363-883, Republic of Korea, Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea, College of Pharmacy, Korea University, Chochiwon, Yeongi, Chungnam 339-700, Republic of Korea
Published online on: September 28, 2011 https://doi.org/10.3892/ol.2011.430
Pages: 113-118

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Abstract

The aim of this study was to investigate the anti-tumor activity of KBH-A42, a novel synthetic histone deacetylase (HDAC) inhibitor. KBH-A42 was shown to significantly suppress the proliferation of all 14 human cancer cell lines tested. Among these cell lines, the human leukemia cell line K562 was the most sensitive, whereas the UM-UC-3 bladder cancer cells were the least sensitive. Additionally, in a human tumor xenograft model using Balb/c nude mice, KBH-A42 was shown to significantly inhibit the growth of K562 tumors, although it only slightly inhibited the growth of UM-UC-3 tumors. The results of flow cytometry analysis and caspase 3/7 activation assays showed that the growth inhibition of K562 cells by KBH-A42 was mediated, at least in part, by the induction of apoptosis, but its growth inhibitory effects on UM-UC-3 cells were not mediated by apoptotic induction. In an effort to gain insight into the mechanism by which KBH-A42 inhibits the growth of cancer cells, a microarray analysis was conducted. Four genes were selected from the genes that were down-regulated or up-regulated by KBH-A42 and confirmed via reverse transcription-polymerase chain reaction as follows: Harakiri (HRK), tumor necrosis factor receptor superfamily, member 10b (TNFRSF10B), PYD and CARD domain containing protein gene (PYCARD) and tumor necrosis factor receptor superfamily, member 8 (TNFRSF8). Collectively, the in vitro and in vivo results suggested that KBH-A42 exhibits anti‑cancer activity, but various types of cells may be regulated differentially by KBH-A42.

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