Histone deacetylase inhibitors in programmed cell death and cancer therapy.
Histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA), are targeted anticancer agents that have significant anticancer activity at doses well tolerated by patients. Recently, we found that HDAC inhibitors can trigger both mitochondria-mediated apoptosis and caspase-independent autophagic cell death, indicating potential benefit of HDAC inhibitors in treating cancers with apoptotic defects. We also found that thioredoxin (TRX) might play a significant role in HDAC inhibitor-induced cell death, and HDAC inhibitors increase TRX levels in normal cells but not transformed cells, which is likely to be one of the reasons why HDAC inhibitors preferentially kill cancer cells. In this review, we discuss the study of HDAC inhibitors in cell death and cancer research, the implications of our recent findings, and some outstanding questions that need to be addressed.
Marks
Paul A
PA
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. marksp@mskcc.org
Jiang
Xuejun
X
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology*; D017382:Reactive Oxygen Species; D013879:Thioredoxins / Q000737:chemistry; D000077337:Vorinostat
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D000077337:Vorinostat