Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG

Abstract

Frequent consumption of green tea, one of the most popular and widely consumed beverages, has been known to protect against development of various cancers according to numerous experimental and several population-based studies. Molecular mechanisms underlying chemopreventive effects exerted by green tea and its components have been extensively investigated. (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to induce expression of glutathione S-transferase, glutathione peroxidase, glutamate cysteine ligase, hemeoxygenase-1, etc. that are involved in the elimination or inactivation of reactive oxygen species and electrophiles implicated in multi-stage carcinogenesis. The redox-sensitive transcription factor, nuclear factor erythroid 2 p45 (NF-E2)-related factor (Nrf2) plays a key role in regulating induction of phase II detoxifying or antioxidant enzymes. Thus, activation of Nrf2 is considered to be an important molecular target of many chemopreventive and chemoprotective agents. This review summarizes the molecular basis of chemoprevention and cytoprotection afforded by EGCG with emphasis on its ability to modulate Nrf2-mediated cellular events.