Plant polyphenols and tumors: From mechanisms to therapies, prevention, and protection against toxicity of anti-cancer treatments

Polyphenolic molecules produced by higher plants in response to biotic and abiotic stresses exert numerous effects on tumorigenic cell transformation, and on tumor cells in vitro and in vivo, and may interact with conventional antitumor therapies. In the present review, we collected and critically discussed data on: (i) redox-dependent and redoxindependent mechanisms underlying cytotoxic/cytostatic effects of PPs and their metabolites towards tumor cells and cytoprotection of normal cells; (ii) mechanisms of anti-angiogenic and anti-metastatic action of PPs; (iii) PPs-associated phototoxicity against tumor cells and photoprotection of non-tumor cells; (iv) PPs effects on drug-metabolizing enzymes as a basis for their synergism or antagonism with chemotherapy; (v) molecular pathways leading to tumor chemoprevention by PPs; and (vi) PPs as protectors against toxic effects of chemo-, radio-, and photodynamic therapies.