Class IIb HDAC Inhibition Enhances the Inhibitory Effect of Am80, a Synthetic Retinoid, in Prostate Cancer
| Autor: | Hiroyuki Kagechika, Mari Ishigami-Yuasa, Hisao Ekimoto |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Methyltransferase Tetrahydronaphthalenes Pyridines Receptors Retinoic Acid Pharmaceutical Science Antineoplastic Agents Decitabine Benzoates 03 medical and health sciences chemistry.chemical_compound Prostate cancer 0302 clinical medicine Cell Line Tumor LNCaP medicine Humans Pharmacology Sulfonamides Vorinostat Chemistry Cancer Prostatic Neoplasms Drug Synergism General Medicine medicine.disease Androgen receptor Gene Expression Regulation Neoplastic Histone Deacetylase Inhibitors Retinoic acid receptor 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Tamibarotene Drug Therapy Combination Histone deacetylase |
| Zdroj: | Biologicalpharmaceutical bulletin. 42(3) |
| ISSN: | 1347-5215 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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