title: Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen species.
abstract: Catechins, the dietary phytochemicals present in green tea and other beverages, are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. While it is believed that the antioxidant properties of catechins and related dietary agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, these properties cannot account for apoptosis induction and chemotherapeutic observations. Catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) are the four major constituents of green tea. In this article, using human peripheral lymphocytes and comet assay, we show that C, EC, EGC and EGCG cause cellular DNA breakage and can alternatively switch to a prooxidant action in the presence of transition metals such as copper. The cellular DNA breakage was found to be significantly enhanced in the presence of copper ions. Catechins were found to be effective in providing protection against oxidative stress induced by tertbutylhydroperoxide, as measured by oxidative DNA breakage in lymphocytes. The prooxidant action of catechins involved production of hydroxyl radicals through redox recycling of copper ions. We also determined that catechins, particularly EGCG, inhibit proliferation of breast cancer cell line MDA-MB-231 leading to a prooxidant cell death. Since it is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies, cancer cells would be more subject to redox cycling between copper ions and catechins to generate reactive oxygen species (ROS) responsible for DNA breakage. Such a copper dependent prooxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells.
authors: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202002, India. farhan@mohdfarhan.com.
authors: Mohd
authors: M
authors: Farhan
authors: UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Birkat Al Mauz, PO Box 33, Postal Code 616, Nizwa, Oman. husainyar@gmail.com.
authors: Husain Yar
authors: HY
authors: Khan
authors: Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah 21589, Saudi Arabia. owais.micro@gmail.com.
authors: Mohammad
authors: M
authors: Oves
authors: UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Birkat Al Mauz, PO Box 33, Postal Code 616, Nizwa, Oman. aharrasi@unizwa.edu.om.
authors: Ahmed
authors: A
authors: Al-Harrasi
authors: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202002, India. nida.rehmani4@gmail.com.
authors: Nida
authors: N
authors: Rehmani
authors: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202002, India. arifkap@gmail.com.
authors: Hussain
authors: H
authors: Arif
authors: Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202002, India. ahmada@karmanos.org.
authors: Sheikh Mumtaz
authors: SM
authors: Hadi
authors: Karmanos Cancer Institute and Wayne State School of Medicine, Detroit, MI 48201, USA. smhadi1946@gmail.com.
authors: Aamir
authors: A
authors: Ahmad
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D003300:Copper / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D010084:Oxidation-Reduction; D013481:Superoxides / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D017665:Hydroxyl Radical; D003300:Copper; D002392:Catechin; D004247:DNA; C427203:calf thymus DNA
keywords: DNA breakage; anticancer; catechins; copper; epicatechin; epigallocatechin; epigallocatechin-3-gallate; prooxidant; reactive oxygen species