NYU Cancer Institute, New York University School of Medicine, Manhattan VAMC, New York, NY 10010, USA.
Int J Oncol. 2010 Sep;37(3):533-9. doi: 10.3892/ijo_00000702.
Prostate cancer is one of the most commonly diagnosed cancers in men. The number of affected men is expected to rapidly increase as the population of males over the age of 50 grows worldwide. For patients who are not cured by local treatment and experience metastatic disease, neither androgen ablation nor chemotherapy can abrogate progression and death from androgen-independent/hormone-refractory disease. Therefore, finding strategies for the prevention of prostate cancer initiation and disease progression is a medical challenge. Consumption of cruciferous vegetables has been reported to be associated with reduced incidence of prostate cancer cases. The isothiocyanates, including phenethyl isothiocyanate (PEITC), from cruciferous vegetables have been demonstrated as active components responsible for chemoprevention. In this review, we summarize the recent findings of PEITC on prostate cancer prevention with an emphasis on epigenetic mechanisms. Studies have indicated that PEITC mediates gene regulation, such as downregulation of androgen receptor expression and induction of endogenous cyclin-dependent kinase inhibitors, p21 and p27. The gene for detoxifying enzyme pi-class glutathione S-transferase (GSTP1), silenced in the vast majority of prostate tumor cells, could be reactivated and the enzymatic function recovered. This may be through epigenetic mechanisms as PEITC is a dual inhibitor of histone deacetylases and aberrant CpG island methylation of various genes. The epigenetic regulation may play a critical role, along with interactive mechanisms including the disruption of microtubule polymerization, in prostate cancer prevention by PEITC. These mechanisms target and correct the aberrations fundamental to the initiation and progression of carcinogenesis in cells, and restoring the cells to a more normal state. Inhibiting and eliminating cancer cells forms the basis of cancer prevention.
前列腺癌是男性最常见的癌症之一。随着全球 50 岁以上男性人口的增长，预计受影响的男性人数将迅速增加。对于局部治疗未治愈且发生转移性疾病的患者，雄激素剥夺或化疗均不能阻止雄激素非依赖/激素难治性疾病的进展和死亡。因此，寻找预防前列腺癌发生和疾病进展的策略是一个医学挑战。有报道称，十字花科蔬菜的消费与前列腺癌病例发病率降低有关。来自十字花科蔬菜的异硫氰酸盐，包括苯乙基异硫氰酸酯（PEITC），已被证明是负责化学预防的活性成分。在这篇综述中，我们总结了最近关于 PEITC 预防前列腺癌的研究结果，重点介绍了表观遗传机制。研究表明，PEITC 介导基因调控，如下调雄激素受体表达和诱导内源性细胞周期蛋白依赖性激酶抑制剂 p21 和 p27。解毒酶 pi 类谷胱甘肽 S-转移酶（GSTP1）的基因在绝大多数前列腺肿瘤细胞中被沉默，可能被重新激活并恢复酶功能。这可能是通过表观遗传机制实现的，因为 PEITC 是组蛋白去乙酰化酶和各种基因异常 CpG 岛甲基化的双重抑制剂。表观遗传调控可能与包括微管聚合破坏在内的相互作用机制一起，在 PEITC 预防前列腺癌中发挥关键作用。这些机制针对并纠正了细胞癌变起始和进展的根本异常，使细胞恢复到更正常的状态。抑制和消除癌细胞是癌症预防的基础。
