Biological and Pharmaceutical Bulletin

Featured article

Volume 42 (2019) Issue 3 Pages 448-452

Class IIb HDAC Inhibition Enhances the Inhibitory Effect of Am80, a Synthetic Retinoid, in Prostate Cancer

Mari Ishigami-Yuasa, Hisao Ekimoto, Hiroyuki Kagechika

Combination therapy is often an effective strategy to treat cancer. In this study, we examined the growth-inhibitory effects of Am80 (tamibarotene), a specific retinoic acid receptor (RAR) α/β agonist, in combination with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), or a DNA methyl transferase (DNMT) inhibitor, 5-aza-2′-deoxycytidine, on androgen receptor (AR)-positive and AR-negative prostate cancer cell lines (LNCaP and PC-3, respectively). We found that the combination therapy of SAHA and Am80 showed an enhanced growth-inhibitory effect on LNCaP cells. Further studies with various HDAC isotype-selective inhibitors showed that SAHA and KD5170 (a selective class I and II HDAC inhibitor) each increased the RARα protein level in LNCaP cells. Our results indicate that the target of the enhancing effect belongs to the Class IIb HDACs, especially HDAC6. Dual targeting of Class IIb HDAC and RARα may be a candidate therapeutic strategy for prostate cancer.

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The growth-inhibitory effects of Am80 (tamibarotene), a specific retinoic acid receptor (RAR) α/β agonist, in combination with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA) on androgen receptor positive or negative prostate cancer cell lines were investigated. Ishigami-Yuasa et al. found that the combination therapy of Am80 and SAHA showed an enhanced growth-inhibitory effect on LNCaP cells. Studies with various HDAC isotype-selective inhibitors indicated that the Class IIb HDACs, especially HDAC6, had significant roles in the enhanced effect of the combination. Thus, dual targeting of Class IIb HDAC and RARα would be useful therapeutic strategy for prostate cancer.

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2019 Volume 42 Issue 3

Prediction of Human Hepatic Clearance for Cytochrome P450 Substrates via a New Culture Method Using the Collagen Vitrigel Membrane Chamber and Fresh Hepatocytes Isolated from Liver Humanized Mice Ryuji Watari, Motoharu Kakiki, Chihiro Yamasaki, Yuji Ishida, Chise Tateno, Yukie Kuroda, Seiichi Ishida, Kazutomi Kusano
Fucoidan Promotes Apoptosis and Inhibits EMT of Breast Cancer Cells Xinjia He, Meilan Xue, Shu Jiang, Weiwei Li, Jinming Yu, Shuai Xiang
Adherence and Concomitant Medication Use among Patients on Warfarin Therapy: Insight from a Large Pharmacy Dispensing Database in Japan Masato Takeuchi, Sayuri Nakano, Sachiko Tanaka-Mizuno, Chika Nishiyama, Yuko Doi, Masaru Arai, Yosuke Fujii, Toshiyuki Matsunaga, Koji Kawakami
A Direct Quantitative Analysis of Erythrocyte Intracellular Ionized Magnesium in Physiological and Pathological Conditions Wenxiang Xiong, Yaru Liang, Xue Li, Guosong Liu, Zhao Wang

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