Induction of apoptosis and histone hyperacetylation by diallyl disulfide in prostate cancer cell line PC-3
Induction of apoptosis and histone hyperacetylation by diallyl disulfide in prostate cancer cell line PC-3
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DOI：
10.1016/j.canlet.2006.11.001
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发表时间：
2007-06-18
期刊：
影响因子：
9.7
通讯作者：
Arunakaran, Jagadeesan
中科院分区：
文献类型：
--
作者：
Arunkumar, Arumugam;Vijayababu, Marati Radhakrishnan;Arunakaran, Jagadeesan
前列腺癌是男性中最具侵袭性和最常见的癌症。在初始阶段，它是雄激素依赖的，雄激素消融治疗在这个阶段是有效的。在最后阶段，它变得不依赖雄激素，对雄激素消融治疗无反应。在这个阶段，诱导细胞凋亡被认为是更好的控制癌症的策略。历史乙酰化和去乙酰化分别参与转录激活和转录抑制。双烯丙基二硫醚（DADS）诱导的历史性超乙酰化可能与抗增殖基因的表达相关。DADS诱导细胞凋亡与组蛋白乙酰化有关。本研究在体外研究了大蒜油溶性有机硫化合物DADS对前列腺癌细胞组蛋白乙酰化和诱导凋亡的影响。annexin V-FITC结合实验证实了其诱导凋亡的作用。通过检测caspase-3的活性来评估细胞凋亡程度。结果表明，DADS诱导前列腺癌细胞凋亡呈剂量依赖性。在25和40 μ M浓度下，DADS增加了早期和晚期凋亡细胞的数量。在DADS处理的细胞中也观察到组蛋白超乙酰化。结论DADS通过影响前列腺癌细胞组蛋白乙酰化诱导细胞凋亡。2006爱思唯尔爱尔兰有限公司版权所有。
Prostate cancer is the most invasive and frequently occurred cancer in men. In the initial stages, it is androgen dependent and the androgen ablation therapy is effective at this stage. In the final stages, it becomes androgen-independent and is unresponsive to androgen ablation therapy. At this stage, induction of apoptosis is considered as a better strategy to control cancer. Historic acetylation and deacetylation are involved in transcriptional activation and transcriptional repression, respectively. Diallyl disulfide (DADS) induced historic hyperacetylation can be correlated with the expression of antiproliferative genes. Induction of apoptosis by DADS has been correlated with histone acetylation. In the present study, DADS, oil soluble organosulfur compound of garlic, has been studied for its effect on histone acetylation and induction of apoptosis in prostate cancer cells in vitro. The induction of apoptosis has been demonstrated by annexin V-FITC binding assay. Extent of apoptosis has been assessed measuring the activity of caspase-3. The results have shown that DADS induced apoptosis in prostate cancer cells in a dose dependent manner. At both 25 and 40 mu M concentrations, DADS increased the number of both early and late apoptotic cells. Histone hyperacetylation was also observed in DADS treated cells. It is concluded that DADS, induces apoptosis by influencing histone acetylation in prostate cancer cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.