A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells
A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells
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DOI：
10.1016/j.ygyno.2007.08.098
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发表时间：
2008-01-01
影响因子：
4.7
通讯作者：
Kim, Hyung Sik
中科院分区：
文献类型：
--
作者：
Ahn, Mee Young;Jung, Jee H.;Kim, Hyung Sik
Objective.组蛋白去乙酰化酶（HDAC）抑制剂是一类很有前途的新型抗癌药物，其通过抑制细胞增殖和诱导各种癌细胞的细胞周期停滞而起作用。Psammaplin A（PsA）是从海绵中分离得到的一种酚类天然产物，被认为是一种很有前途的新型HDAC抑制剂。然而，PsA作为HDAC抑制剂的确切机制知之甚少。本研究探讨了PsA对人子宫内膜癌细胞的抗肿瘤作用。观察PsA对石川子宫内膜癌细胞增殖、细胞周期和凋亡的影响。PsA可明显抑制石川细胞的增殖，并呈剂量依赖性。PsA明显诱导乙酰化H3和H4组蛋白的表达。此外，PsA还能显著上调细胞周期蛋白依赖性激酶抑制因子p21（WAF 1）的表达，下调pRb、cyclins和CDKs的表达，诱导细胞周期阻滞。细胞周期分析显示，PsA处理后G 0/G1和G2/M期细胞比例增加，S期细胞比例降低。PsA处理导致显著的凋亡诱导，这与p53非依赖性p21（WAF 1）表达有关。提示PsA可能通过选择性诱导细胞周期阻滞和凋亡相关基因的表达而发挥抗子宫内膜癌细胞增殖的作用。(c)2007爱思唯尔公司All rights reserved.
Objective. Histone deacetylase (HDAC) inhibitors are promising new class of anticancer agents that act by inhibiting cell proliferation and inducing cell cycle arrest of various cancer cells. Psammaplin A (PsA) is a phenolic natural product that has been isolated from marine sponges, and has been suggested to be a promising novel HDAC inhibitor. However, the precise mechanism of PsA as a HDAC inhibitor is poorly understood. This study investigated the anti-tumor effect of PsA on endometrial human cancer cells.Methods. The cell proliferation, cell cycle, and apoptosis were measured in Ishikawa endometrial cancer cells after PsA treatment.Results. PsA significantly inhibited the proliferation of Ishikawa cells in a dose-dependent manner. PsA markedly induced the expression of acetylated H3 and H4 histone proteins. In addition, PsA markedly up-regulated the expression of cyclin-dependent kinase inhibitor, p21(WAF1), and down-regulated the expression of pRb, cyclins, and CDKs, which lead to induce cell cycle arrest. Cell cycle analysis indicated that PsA treatment increased the proportion of cells in the G0/G1 and G2/M phases, and decreased the ratio of cells in the S phase.Conclusion. The PsA treatment resulted in the significant induction of apoptosis, which was associated with p53 independent p21(WAF1) expression. These results suggest that PsA exhibits the antiproliferative effects on endometrial cancer cells through selective induction of genes related to cell cycle arrest and apoptosis. (c) 2007 Elsevier Inc. All rights reserved.