論文 - 詳細
| RRC ID | 54897 |
|---|---|
| 著者 | Ishigami-Yuasa M, Ekimoto H, Kagechika H. |
| タイトル | Class IIb HDAC Inhibition Enhances the Inhibitory Effect of Am80, a Synthetic Retinoid, in Prostate Cancer. |
| ジャーナル | Biol Pharm Bull |
| Abstract |
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. |
| 巻・号 | 42(3) |
| ページ | 448-452 |
| 公開日 | 2019-1-1 |
| DOI | 10.1248/bpb.b18-00782 |
| PMID | 30828077 |
| MeSH | Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacokinetics Antineoplastic Agents / therapeutic use Benzoates / administration & dosage Benzoates / pharmacokinetics Benzoates / therapeutic use* Cell Line, Tumor Decitabine / administration & dosage Decitabine / pharmacology* Drug Synergism Drug Therapy, Combination Gene Expression Regulation, Neoplastic / drug effects Histone Deacetylase Inhibitors / administration & dosage Histone Deacetylase Inhibitors / pharmacology Humans Male Prostatic Neoplasms / drug therapy* Pyridines / administration & dosage Pyridines / pharmacology* Receptors, Retinoic Acid / genetics Receptors, Retinoic Acid / metabolism Sulfonamides / administration & dosage Sulfonamides / pharmacology* Tetrahydronaphthalenes / administration & dosage Tetrahydronaphthalenes / pharmacokinetics Tetrahydronaphthalenes / therapeutic use* Vorinostat / administration & dosage Vorinostat / pharmacology* |
| IF | 1.54 |
| 引用数 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-3(RCB2145) |