异硫氰酸苯己酯诱导前列腺癌细胞生长抑制的表观遗传机制
Epigenetic mechanism of growth inhibition induced by phenylhexyl isothiocyanate in prostate cancer cells.
作者信息
Beklemisheva Anastasia A, Fang Yuqiang, Feng Jingyang, Ma Xudong, Dai Wei, Chiao Jen Wei
机构信息
Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
出版信息
Anticancer Res. 2006 Mar-Apr;26(2A):1225-30.
BACKGROUND
Isothiocyanates, the constituents of cruciferous vegetables, may be able to prevent prostate cancer. The hypothesis that they could remodel chromatins and activate cell cycle inhibitors, such as p21 for growth inhibition, was tested.
MATERIALS AND METHODS
Prostate cancer LNCaP cells were exposed to phenylhexyl isothiocyanate (PHI). The status of histone acetylation and the activity of histone deacetylases (HDAC) were investigated. The association of p21 with hyperacetylated histones was examined by chromatin immunoprecipitation.
RESULTS
The PHI-exposed LNCaP cells had diminished activity of HDAC 1 and 2. Global and selective histone acetylation was enhanced, consistent with the signs of chromatin unfolding. The hyperacetylated histones increased accessibility to the p21 promoter for transcription, leading to G1 arrest and apoptosis.
CONCLUSION
PHI inhibited the activity of HDAC and remodeled chromatins to activate p21 for cell cycle arrest, underlying an epigenetic mechanism regulating the growth of prostate cancer cells.
背景
异硫氰酸盐是十字花科蔬菜的成分，可能具有预防前列腺癌的作用。本研究对它们能够重塑染色质并激活细胞周期抑制剂（如p21以抑制生长）这一假说进行了验证。
材料与方法
将前列腺癌LNCaP细胞暴露于苯己基异硫氰酸盐（PHI）中。研究组蛋白乙酰化状态和组蛋白脱乙酰酶（HDAC）的活性。通过染色质免疫沉淀法检测p21与高乙酰化组蛋白的关联。
结果
暴露于PHI的LNCaP细胞中HDAC 1和2活性降低。整体和选择性组蛋白乙酰化增强，这与染色质解折叠的迹象一致。高乙酰化组蛋白增加了p21启动子转录的可及性，导致G1期阻滞和细胞凋亡。
结论
PHI抑制HDAC的活性并重塑染色质以激活p21从而使细胞周期停滞，这是一种调节前列腺癌细胞生长的表观遗传机制。
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