Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Feb 26, 2016; 7(1): 88-99
Published online Feb 26, 2016. doi: 10.4331/wjbc.v7.i1.88
Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals: From experimental models to clinical trials
Girish B Maru, Rasika R Hudlikar, Gaurav Kumar, Khushboo Gandhi, Manoj B Mahimkar
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
Author contributions: Maru GB contributed to conception and design of the review/MS; Maru GB, Hudlikar RR, Kumar G, Gandhi K and Mahimkar MB contributed to acquisition of data or analysis, interpretation of data, drafting the article or making critical revisions and final approval of the version of the article to be published.
Conflict-of-interest statement: All authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Girish B Maru, PhD, Honorary Consultant, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Sector-22, Kharghar, Navi Mumbai 410210, India. gmaru@actrec.gov.in
Telephone: +91-22-27405022 Fax: +91-22-27405085
Received: June 29, 2015
Peer-review started: July 4, 2015
First decision: August 25, 2015
Revised: October 20, 2015
Accepted: November 23, 2015
Article in press: November 25, 2015
Published online: February 26, 2016
Abstract

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.

Keywords: Cancer prevention, Dietary phytochemicals, Chemoprevention, Experimental efficacy, Mechanisms of action, Clinical trials, Bioavailability, Toxicity

Core tip: Review compares the available evidence on the chemopreventive efficacy and probable mechanisms of chemoprevention by selected dietary phytochemicals in experimental systems and clinical trials. All the dietary phytochemicals covered have demonstrated chemopreventive efficacy against carcinogen-induced tumors in rodents at several organ sites. Mechanism of observed chemopreventive action(s) involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases leading to effects on multiple genes and cell signaling pathways. Clinical trials with these compounds have not demonstrated their chemopreventive efficacy. Probable reasons for observed mismatch between the two systems and areas of current research efforts and recommendations have been presented.