Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Düsseldorf, Switzerland.
Eur J Cancer Prev. 2012 Jan;21(1):55-64. doi: 10.1097/CEJ.0b013e32834a7e6f.
Various antiepileptic drugs such as valproic acid, carbamazepine, oxcarbazepine, lamotrigine and levetiracetam are known to exert histone deacetylase inhibitory (HDACi) properties, which can modify aberrantly silenced gene expression by an epigenetic mechanism. This study was initiated to examine a potential beneficial effect of these drugs on prostate cancer (PC) development. The prostate-specific antigen (PSA) levels of 106 patients under long-term treatment with antiepileptic drugs and known HDACi properties were examined. PSA represents a hallmark in the early detection of PC, and its levels may predict an invasive disease in subsequent years. For in-vitro experiments, the PC cell line LNCaP was treated with HDACi drugs; subsequently, PSA and further PC markers were assessed. When men over 50 years of age were treated with HDACi drugs they had lower age-corrected PSA levels compared with control groups, according to the following ranking: valproic acid>levetiracetam>carbamazepine/oxcarbazepine>lamotrigine. Furthermore, there was a correlation between PSA reduction and the number of HDACi drugs within the medication, lending credence to the idea that a synergistic effect might be possible. Moreover, in vitro, HDACi drugs decrease PSA on mRNA and protein levels and exhibit further oncoprotective properties.The fact that HDACi drugs exert antiproliferative effects on neoplastic cells in vitro and in vivo, which are paralleled by expression alterations of aberrantly regulated genes, underlines the potential therapeutic value of HDACi drugs. These data suggest that long-term HDACi treatment can positively influence the characteristically slow transformation of tumour precursor cells in the prostate and may thus reduce a patient's risk of developing PC.
各种抗癫痫药物，如丙戊酸、卡马西平、奥卡西平、拉莫三嗪和左乙拉西坦，已知具有组蛋白去乙酰化酶抑制（HDACi）特性，可通过表观遗传机制修饰异常沉默的基因表达。本研究旨在探讨这些药物对前列腺癌（PC）发展的潜在有益作用。检查了 106 名长期接受抗癫痫药物治疗且已知具有 HDACi 特性的患者的前列腺特异性抗原（PSA）水平。PSA 是前列腺癌早期检测的一个标志，其水平可预测随后几年的侵袭性疾病。在体外实验中，用 HDACi 药物处理 PC 细胞系 LNCaP；随后，评估了 PSA 和其他 PC 标志物。当 50 岁以上的男性用 HDACi 药物治疗时，与对照组相比，他们的年龄校正 PSA 水平较低，按以下顺序排列：丙戊酸>左乙拉西坦>卡马西平/奥卡西平>拉莫三嗪。此外，PSA 降低与药物中 HDACi 药物的数量之间存在相关性，这表明可能存在协同作用。此外，在体外，HDACi 药物可降低 PSA 在 mRNA 和蛋白质水平上的表达，并表现出进一步的致癌保护特性。事实上，HDACi 药物在体外和体内对肿瘤细胞具有抗增殖作用，同时伴有异常调节基因的表达改变，这突出了 HDACi 药物的潜在治疗价值。这些数据表明，长期 HDACi 治疗可以积极影响前列腺中肿瘤前体细胞特征性缓慢的转化，从而降低患者患 PC 的风险。
