World Journal of Biological Chemistry, 2016, 7(1):88-99.

Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: From experimental models to clinical trials

Girish B Maru, Rasika R Hudlikar, Gaurav Kumar, et al

Girish B Maru, Rasika R Hudlikar, Gaurav Kumar, Khushboo Gandhi, Manoj B Mahimkar, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai 410210, India.

Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals (capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-induced experimental tumors and/or associated biomarkers and processes in rodents at several organ sites. The observed anti-initiating, anti-promoting and anti-progression activity of dietary phytochemicals in carcinogen-induced experimental models involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases resulting to effects on multiple genes and cell signaling pathways. Results from clinical trials using these compounds have not shown them to be chemopreventive. This may be due to our: (1) inability to reproduce the exposure conditions, i.e., levels, complexity, other host and lifestyle factors; and (2) lack of understanding about the mechanisms of action and agent-mediated toxicity in several organs and physiological processes in the host. Current research efforts in addressing the issues of exposure conditions, bioavailability, toxicity and the mode of action of dietary phytochemicals may help address the reason for observed mismatch that may ultimately lead to identification of new chemopreventive agents for protection against broad spectrum of exposures.

中国《世界生物化学杂志》, 2016, 7(1):88-99.

认识膳食植物化学物质预防癌症的分子机制：从实验模型到临床试验

Girish B Maru，Rasika R Hudlikar，Gaurav Kumar，Khushboo Gandhi，Manoj B Mahimkar，癌症治疗，研究和教育高级中心（ACTREC），塔塔纪念中心（TMC），Kharghar，Navi Mumbai 410210，印度。

化学预防是癌症预防的方法之一，目的是来延缓或中断多个通路和多个步骤在癌症过程中，即癌症的启动、促进和进展。在环境化学预防化合物中，饮食/饮料衍生的组分正在研究中，由于其长久的暴露于人类、 高耐受性，毒性低和报告的生物活动。本文章简要介绍并比较了选定的膳食植物化学物质（辣椒素，姜黄素，二烯丙基硫化物，染料木素，绿茶/红茶多酚，吲哚，番茄红素，异氰酸苯乙酯，白藜芦醇，类视黄醇和生育酚）在实验系统和临床试验的化学预防功效和化学预防的可能机制。本综述中涵盖的所有膳食植物化学物质已经证实了在啮齿动物的多个器官部位中对自发或致癌物诱导的实验性肿瘤和/或相关生物标志物和过程有化学预防功效。膳食植物化学物质在致癌物诱导的实验模型中观察到的抗引发，抗促进和抗进展活性涉及植物化学介导的氧化还原变化，酶和信号激酶的调节，导致对多种基因和细胞信号传导途径均有影响。从使用这些化合物的临床试验结果来看，他们不显示是化学预防的。这可能是由于：(1) 未能重现观测条件，即水平、 复杂性、 其它主机和生活方式的因素; （2）对于宿主中几种器官和生理过程的作用机制和药剂介导的毒性缺乏了解。当前研究努力解决的问题是曝光条件、 生物利用度、毒性和膳食的植物化学物质作用的原理，这些可以帮助解决观察结果不匹配的原因，这可能导致最终找到用于保护的广谱化学预防药物。