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

• Published in: Molecular nutrition & food research 2014-03, Vol.58 (3), p.437-446
• Main Authors: Khan, Husain Yar, Zubair, Haseeb, Faisal, Mohd, Ullah, Mohd Fahad, Farhan, Mohd, Sarkar, Fazlul H, Ahmad, Aamir, Hadi, Sheikh Mumtaz
• Format: Article
• Language: English
• Subjects: Anticancer; Anticarcinogenic Agents - pharmacology; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; antioxidants; apigenin; Apigenin - pharmacology; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Death - drug effects; Cell Line, Tumor - drug effects; cell proliferation; Cell Proliferation - drug effects; chelating agents; Chelating Agents - pharmacology; Chemical agents; Chemical and industrial products toxicology. Toxic occupational diseases; chemical structure; chemoprevention; Chemotherapy; Copper; Copper - metabolism; cytotoxicity; Drug Screening Assays, Antitumor; epithelial cells; Feeding. Feeding behavior; fruits; functional foods; Fundamental and applied biological sciences. Psychology; growth retardation; Humans; ions; luteolin; Luteolin - pharmacology; Medical sciences; Metals and various inorganic compounds; Pharmacology. Drug treatments; Phenanthrolines - pharmacology; Polyphenols; Polyphenols - pharmacology; Prooxidant; Reactive oxygen species; Reactive Oxygen Species - metabolism; resveratrol; spices; Stilbenes - pharmacology; Toxicology; Tumors; vegetables; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201300417

SCOPE: 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. METHODS AND 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. CONCLUSION: 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.