+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen species



Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen species



Toxins 8(2): 37



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057349432

Download citation: RISBibTeXText

PMID: 26861392

DOI: 10.3390/toxins8020037


Related references

Catalytic therapy of cancer by ascorbic acid involves redox cycling of exogenous/endogenous copper ions and generation of reactive oxygen species. ChemoTherapy 56(4): 280-284, 2010

Flavonoids-induced redox cycling of copper ions leads to generation of reactive oxygen species: A potential role in cancer chemoprevention. International Journal of Biological Macromolecules 106: 569-578, 2017

Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species. Bmc Cancer 14: 527, 2015

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. Molecular Nutrition and Food Research 58(3): 437-446, 2015

Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) by PAH o-quinones: involvement of reactive oxygen species and copper(II)/copper(I) redox cycling. Chemical Research in Toxicology 18(6): 1026-1037, 2005

Generation of reactive oxygen species by the redox cycling of nitroprusside. Biochimica Et Biophysica Acta. 1289(2): 202, 1996

Redox cycling and generation of reactive oxygen species in commercial infant formulas. Food Chemistry 196: 189-195, 2016

Bio-inspired redox-cycling antimicrobial film for sustained generation of reactive oxygen species. Biomaterials 162: 109-122, 2018

Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalyzed redox cycling of flavonoids. Chemical Research in Toxicology 12(6): 521-525, 1999

Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species. Molecular Nutrition and Food Research 55(4): 553-559, 2011

NADH-dependent generation of reactive oxygen species by microsomes in the presence of iron and redox cycling agents. Biochemical Pharmacology 42(3): 529-535, 1991

Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper-thiosemicarbazone complexes. Journal of Biological Inorganic Chemistry 21(3): 407-419, 2017

Menadione-induced reactive oxygen species generation via redox cycling promotes apoptosis of murine pancreatic acinar cells. Journal of Biological Chemistry 281(52): 40485-40492, 2006

Synergistic interactions between nadh ferritin and redox cycling agents in generation of reactive oxygen species implications for alcohol toxicity. Alcoholism Clinical & Experimental Research 14(2): 307, 1990

Dithiocarbamate toxicity toward thymocytes involves their copper-catalyzed conversion to thiuram disulfides, which oxidize glutathione in a redox cycle without the release of reactive oxygen species. Archives of Biochemistry and Biophysics 353(1): 73-84, 1998