Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells.
Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells.
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DOI：
10.1002/mnfr.201000547
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发表时间：
2011-07
影响因子：
5.2
通讯作者：
Ho, Emily
中科院分区：
文献类型：
--
作者：
Clarke, John D.;Hsu, Anna;Yu, Zhen;Dashwood, Roderick H.;Ho, Emily
萝卜硫烷（SFN）是一种异硫氰酸酯，来源于十字花科蔬菜，如花椰菜。SFN抑制组蛋白脱乙酰酶的能力可能是其作为化学预防剂的一种机制。化学预防剂在癌症而不是正常细胞中特异性引起细胞毒性的能力是确定其安全性和临床相关性的重要因素。我们表征了SFN在正常（PrEC）、良性增生（BPH1）和癌性（LnCap和PC3）前列腺上皮细胞中的作用。我们观察到15 μM SFN选择性地诱导BPH1、LnCap和PC 3细胞的细胞周期停滞和凋亡，但不诱导PrEC细胞。SFN处理还选择性地降低HDAC活性，以及I类和II类HDAC蛋白，增加P21启动子处的乙酰化组蛋白H3，诱导p21表达并增加前列腺癌细胞中的微管蛋白乙酰化。HDAC6过表达能够逆转SFN诱导的细胞毒性。在PrEC细胞中，SFN仅引起HDAC活性的短暂降低，而测试的任何其他终点均无变化。PrEC和PC3对SFN敏感性的差异可能不是由于SFN代谢的差异或2相酶诱导的差异。从这些数据中，我们得出结论，SFN对正常细胞和癌细胞中的细胞增殖、HDAC活性和下游靶点发挥不同的作用。
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables such as broccoli. The ability of SFN to inhibit histone deacetylase enzymes may be one mechanism by which it acts as a chemoprevention agent. The ability of a chemopreventive agent to specifically cause cytotoxicity in cancer, not normal cells is an important factor in determining its safety and clinical relevance. We characterized the effects of SFN in normal (PrEC), benign hyperplasia (BPH1) and cancerous (LnCap and PC3) prostate epithelial cells. We observed that 15 µM SFN selectively induced cell cycle arrest and apoptosis in BPH1, LnCap and PC3 cells but not PrEC cells. SFN treatment also selectively decreased HDAC activity, and Class I and II HDAC proteins, increased acetylated histone H3 at the promoter for P21, induced p21 expression and increased tubulin acetylation in prostate cancer cells. HDAC6 over-expression was able to reverse SFN-induced cyotoxicity. In PrEC cells, SFN caused only a transient reduction in HDAC activity with no change in any other endpoints tested. The differences in sensitivity to SFN in PrEC and PC3 are likely not due to differences in SFN metabolism or differences in phase 2 enzyme induction. From these data we conclude that SFN exerts differential effects on cell proliferation, HDAC activity and downstream targets in normal and cancer cells.
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影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
4.7
作者：
Jackson, SJT;Singletary, KW
通讯作者：
Singletary, KW
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Li Y;Li X;Guo B
通讯作者：
Guo B
影响因子：
4
作者：
Korkmaz, CG;Fronsdal, K;Saatcioglu, F
通讯作者：
Saatcioglu, F