Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada.
Biomed Pharmacother. 2012 Apr;66(3):232-6. doi: 10.1016/j.biopha.2011.06.007. Epub 2011 Aug 27.
Histone deacetylase (HDAC) inhibitors represent a novel class of drugs that selectively induce cell cycle arrest and apoptosis in transformed cells. This study examined, for the first time, the effects of the relatively new HDAC inhibitor, M344 [4-dimethylamino-N-(6-hydroxycarbamoylhexyl)-benzamide], on the proliferation of MCF-7 breast cancer cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays revealed significant concentration- and time-dependent decreases in MCF-7 cell proliferation following treatment with M344 (1-100μM). In contrast to the significant induction of p21(waf1/cip1) mRNA expression following treatment with M344 (10μM) for 1 or 3 days, there was a significant decrease in p53 mRNA expression, although p53 protein levels were unchanged. Similar treatment with M344 also induced expression of the pro-apoptotic genes, Puma and Bax, together with the morphological features of apoptosis, in MCF-7 cells. The results of this study reinforce previous findings indicating that HDAC inhibitors are an important group of oncostatic drugs, and show that M344 is a potent suppressor of breast cancer cell proliferation.
组蛋白去乙酰化酶 (HDAC) 抑制剂是一类新型药物，能选择性诱导转化细胞的细胞周期停滞和凋亡。本研究首次考察了相对较新的 HDAC 抑制剂 M344 [4-二甲基氨基-N-(6-羟基羰基己基)-苯甲酰胺] 对 MCF-7 乳腺癌细胞增殖的影响。MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐] 检测显示，M344（1-100μM）处理后 MCF-7 细胞增殖出现显著的浓度和时间依赖性降低。与 M344（10μM）处理 1 或 3 天后 p21(waf1/cip1)mRNA 表达显著诱导相反，p53mRNA 表达显著降低，尽管 p53 蛋白水平不变。类似的 M344 处理还诱导 MCF-7 细胞中促凋亡基因 Puma 和 Bax 的表达以及凋亡的形态特征。本研究结果进一步证实了先前的发现，即 HDAC 抑制剂是一类重要的抗肿瘤药物，并表明 M344 是一种有效的乳腺癌细胞增殖抑制剂。
