title: Old wine in a new bottle: the Warburg effect and anticancer mechanisms of resveratrol.
abstract: Resveratrol found in fruits, vegetables and beverages such as red wine, has been extensively evaluated for its anticardiovascular disease and cancer preventive effects. Even though studies have demonstrated its anti-tumor effects, there is still no clear explanation for cancer cell selective mechanisms of action of resveratrol. Initial investigations were focused on its anti-oxidant and cytoprotective mechanism of action, yet, a large number of studies have demonstrated that resveratrol can behave either as anti-oxidant or pro-oxidant depending on the selective microenvironment. What makes resveratrol a protective agent in normal cells and a radical generator possessing cytotoxic activity against cancer cells is a widely debated topic. There must be certain conditions found in tumors that allow resveratrol to become a pro-oxidant that clearly differs from that found in normal cells. Results of studies from our group have established that many different dietary agents can mobilize intracellular copper ions and in the process, generate reactive oxygen species through Fenton type reactions leading to oxidative DNA breakage and consequently, cell death. More significantly, we demonstrated that such pro-oxidant-induced DNA damage and apoptotic activity are enhanced in low pH environments; characteristically observed in tumors due to preferential dependence on glycolysis or the "Warburg effect". This review discusses the recent advancements in understanding the pro-oxidant anti-cancer behavior of resveratrol as a dietary chemopreventive agent, explained in the light of the Warburg effect.
authors.affiliation: Department of Biochemistry, Aligarh Muslim University, India.
authors.forename: Irfana
authors.initials: I
authors.lastname: Muqbil
authors.forename: Frances W J
authors.initials: FW
authors.lastname: Beck
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Ramzi M
authors.initials: RM
authors.lastname: Mohammad
authors.forename: S M
authors.initials: SM
authors.lastname: Hadi
authors.forename: Asfar S
authors.initials: AS
authors.lastname: Azmi
mesh_terms: D000818:Animals; D003300:Copper / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000494:pharmacology* / Q000627:therapeutic use; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D017382:Reactive Oxygen Species; D013267:Stilbenes; D003300:Copper; D000077185:Resveratrol