Marks Paul A, Jiang Xuejun
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cell Cycle. 2005 Apr;4(4):549-51. doi: 10.4161/cc.4.4.1564. Epub 2005 Apr 28.
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.
组蛋白脱乙酰酶（HDAC）抑制剂，如辛二酰苯胺异羟肟酸（SAHA），是靶向抗癌药物，在患者耐受性良好的剂量下具有显著的抗癌活性。最近，我们发现HDAC抑制剂可引发线粒体介导的凋亡和半胱天冬酶非依赖性自噬性细胞死亡，这表明HDAC抑制剂在治疗具有凋亡缺陷的癌症方面具有潜在益处。我们还发现硫氧还蛋白（TRX）可能在HDAC抑制剂诱导的细胞死亡中发挥重要作用，并且HDAC抑制剂可增加正常细胞而非转化细胞中的TRX水平，这可能是HDAC抑制剂优先杀死癌细胞的原因之一。在本综述中，我们讨论了HDAC抑制剂在细胞死亡和癌症研究中的研究、我们最近发现的意义以及一些需要解决的突出问题。
