Cellular, molecular, and biological perspective of polyphenols in chemoprevention and therapeutic adjunct in cancer

Abstract

Emerging evidences from extensive laboratory research backed by epidemiological data lead credence to a family of natural origin compounds with putative chemopreventive potential to intervene ontogeny and progression of cancer. This family of natural compounds called “polyphenols” has more than one phenol unit or building block per molecule and considered beneficial if not critical to human health. Major dietary sources contributing to total polyphenol intake include fruits, vegetables, cereals, chocolates, dry legumes and beverages such as fruit juice, tea, coffee and red wine. Polyphenols have captivated great attention because of their pleiotropic actions including antioxidative, xenobiotic detoxification, anti-inflammatory, and therapeutic benefits including antitumor and chemosensitizing potential to several common cytotoxic chemotherapeutic agents. Mechanistically, polyphenol-rich diet has shown to modulate transcription factors and interrupt the complex cell signaling pathways and their component enzymes, microRNAs, with common aim to thwart tumor cell proliferation while sparing normal cells and inhibits angiogenesis, invasion, and metastasis considered as hallmarks of cancer. This chapter presents a succinct global overview of deregulated signaling pathways, antioxidant status and enzymes exacerbated in tumors and the role of polyphenols in modulating the end results in different sitespecific cancers citing representative examples. We conclude highlighting chemosensitization of cancer with select polyphenol compounds – genistein, epigallocatechin-3-gallate, curcumin, quercetin, silibinin, and resveratrol – along with appraisal on ongoing clinical trials with primary objective of better clinical management of cancer patients with long-term survival benefits and designing novel analogs with improved bioavailability for future use.