title: Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: a mechanism for cancer chemopreventive action.
abstract: METHODS
  Anticancer polyphenolic nutraceuticals from fruits, vegetables, and spices are generally recognized as antioxidants, but can be prooxidants in the presence of copper ions. We earlier proposed a mechanism for such activity of polyphenols and now we provide data in multiple cancer cell lines in support of our hypothesis.
  
  
  RESULTS
  Through multiple assays, we show that polyphenols luteolin, apigenin, epigallocatechin-3-gallate, and resveratrol are able to inhibit cell proliferation and induce apoptosis in different cancer cell lines. Such cell death is prevented to a significant extent by cuprous chelator neocuproine and reactive oxygen species scavengers. We also show that normal breast epithelial cells, cultured in a medium supplemented with copper, become sensitized to polyphenol-induced growth inhibition.
  
  
  CONCLUSIONS
  Since the concentration of copper is significantly elevated in cancer cells, our results strengthen the idea that an important anticancer mechanism of plant polyphenols is mediated through intracellular copper mobilization and reactive oxygen species generation leading to cancer cell death. Moreover, this prooxidant chemopreventive mechanism appears to be a mechanism common to several polyphenols with diverse chemical structures and explains the preferential cytotoxicity of these compounds toward cancer cells.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, India.
authors.forename: Husain Yar
authors.initials: HY
authors.lastname: Khan
authors.forename: Haseeb
authors.initials: H
authors.lastname: Zubair
authors.forename: Mohd
authors.initials: M
authors.lastname: Faisal
authors.forename: Mohd Fahad
authors.initials: MF
authors.lastname: Ullah
authors.forename: Mohd
authors.initials: M
authors.lastname: Farhan
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.forename: Sheikh Mumtaz
authors.initials: SM
authors.lastname: Hadi
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D047311:Luteolin / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D002614:Chelating Agents; D010618:Phenanthrolines; D059808:Polyphenols; D017382:Reactive Oxygen Species; D013267:Stilbenes; D003300:Copper; D047310:Apigenin; C002701:neocuproine; D002392:Catechin; C045651:epigallocatechin gallate; D047311:Luteolin; D000077185:Resveratrol
keywords: Anticancer; Copper; Polyphenols; Prooxidant; Reactive oxygen species