Chemosensitization of Tumor Cells by Phenolic Antioxidants: The Role of the Nrf2 Transcription Factor

Abstract

Pharmacological modification of the redox properties of tumor cells is a promising approach to enhance the efficiency of antitumor therapy. The Nrf2 transcription factor is considered as a new target for the development of selective chemosensitizers. Nrf2 plays a key role in the regulation of cellular redox homeostasis against stress and during adaptation processes. Many natural and synthetic phenolic antioxidants are inducers of Nrf2 transcriptional activity. Because of differences in Nrf2 transcriptional activity between normal and tumor cells, phenolic antioxidants at certain concentrations act as biological regulators of the antioxidant activity, which has two different effects. They promote the development of oxidative stress and enhance the effect of antitumor drugs in tumor cells and exhibit protective properties in the normal cells. This review discusses possible molecular mechanisms of the action and the prospects for clinical use of natural and synthetic phenolic antioxidants in antitumor therapy.