Natural Polyphenols and their Synthetic Analogs as Emerging Anticancer Agents

Abstract

Polyphenols are a structural class of natural and synthetic organic chemicals which contain phenol units. Numerous epidemiological, preclinical and clinical studies have strongly supported their benefical effects for human health. Polyphenols group include molecules of utterly different complexity grades, ranging from simple molecules to highly polymerized structures. They are classified into: Phenolic acids, Flavonoids, Lignans and the less common Stilbenes. This work first intends to review the current studies on classification, chemical composition and metabolism of polyphenols. Then, we have reported cancer preventive and treatment effects of polyphenols, especially focused in the green tea polyphenol (GTP) (-)-Epigallocatechin-3-gallate (EGCG). Polyphenols such as EGCG and their synthetic analogs interfere in carcinogenesis by modulating and regulating multiple signaling pathways and transcription factors, membrane-associated receptor tyrosine kinases (RTKs), fatty acid metabolism and lipid rafts or methylation together with other emerging targets such as proteasome, telomerase and cancer stem cells. Here, we have reviewed several potential molecular targets of polyphenols (mainly EGCG and EGCG analogs) and their anticancer effects in cellular and animal models of different human carcinomas and we have also listed Phases I and II clinical trials conducted to study the antitumor properties of GTPs.

Keywords: Clinical trials; EGCG; FASN; green tea polyphenols; mouse models; receptor tyrosine kinases; signaling pathways; targets..