M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells.
M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells.
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发表时间：
2006
影响因子：
4.7
通讯作者：
N. Takai;T. Ueda;M. Nishida;K. Nasu;H. Narahara
中科院分区：
文献类型：
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作者：
N. Takai;T. Ueda;M. Nishida;K. Nasu;H. Narahara
目的组蛋白去乙酰化酶抑制剂（HDACIs）可抑制细胞增殖，诱导细胞周期阻滞，促进肿瘤细胞凋亡。方法研究新型HDACI（M344）对子宫内膜癌细胞株石川、卵巢癌细胞株SK-OV-3和正常人子宫内膜上皮细胞的作用。用不同浓度的M344处理子宫内膜癌和卵巢癌细胞，研究其对细胞生长、细胞周期、凋亡及相关测量的影响。结果3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四氮唑溴化物实验显示所有子宫内膜癌和卵巢癌细胞系对M344的生长抑制作用敏感，而正常子宫内膜上皮细胞在用诱导子宫内膜癌和卵巢癌细胞生长抑制的相同剂量的M344处理后仍存活。细胞周期分析表明，它们暴露于M344降低了S期细胞的比例，增加了G 0/G1期细胞的比例。细胞凋亡的诱导证实了膜联蛋白V染色的外部化磷脂酰丝氨酸和线粒体的跨膜电位的损失。这种诱导与细胞生长、恶性表型和细胞凋亡相关基因的表达改变同时发生。此外，这些细胞系的M344处理增加了H3和H4组蛋白尾部的乙酰化。结论：这些结果提高了M344在治疗子宫内膜癌和卵巢癌方面特别有效的可能性。
OBJECTIVE Histone deacetylase inhibitors (HDACIs) can inhibit cell proliferation, induce cell cycle arrest, and stimulate apoptosis of cancer cells. METHODS We investigated the effects of a novel synthesized HDACI, M344, on Ishikawa endometrial cancer cell line, SK-OV-3 ovarian cancer cell line, and normal human endometrial epithelial cells. Endometrial and ovarian cancer cells were treated with various concentrations of M344, and its effect on cell growth, cell cycle, apoptosis, and related measurements was investigated. RESULTS 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that all endometrial and ovarian cancer cell lines were sensitive to the growth inhibitory effect of M344, although normal endometrial epithelial cells were viable after the treatment with the same doses of M344 that induced growth inhibition of endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to M344 decreased the proportion of cells in the S-phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. Furthermore, M344 treatment of these cell lines increased acetylation of H3 and H4 histone tails. CONCLUSIONS These results raise the possibility that M344 may prove particularly effective in the treatment of endometrial cancers and ovarian cancers.