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.

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

“…Accordingly, the heartwood extract used in the present study showed the presence of (−)-EC and (±)-C, as outlined by the quantitative analysis performed. Their pharmacological properties, although much less investigated with respect to EGCG, include the capability of inducing apoptosis [40], an effect strictly linked to their prooxidant activity [41][42][43]. Catechins, as previously outlined, can behave as pro-oxidants in the presence of Cu(II), leading to cytotoxic action [41].…”

“…Their pharmacological properties, although much less investigated with respect to EGCG, include the capability of inducing apoptosis [40], an effect strictly linked to their prooxidant activity [41][42][43]. Catechins, as previously outlined, can behave as pro-oxidants in the presence of Cu(II), leading to cytotoxic action [41]. As the cellular copper level is considerably elevated in cancer cells [43,44], it is conceivable that in the present experimental conditions, HT-29 cells may be more subjected to electron transfer between copper ions and AC catechins to generate ROS.…”

“…In the present study, however, AC treatment did not affect caspase-8's activity, thereby confirming that the apoptosis induced in HT-29 cells was mediated via the intrinsic mitochondrial pathway and not via the extrinsic, death receptor-linked caspase-8 pathway. Finally, even though intrinsic apoptotic signalling is potentially triggered by oxidative stress in many catechin-treated cancer cells [40][41][42][43], the possibility that AC activates apoptosis via a ROS-independent mechanism should be studied further.…”

Yeşil çay ve depot-medroxyprogesterone asetat infüzyonunun granüloza hücre sayısı ile ovaryan primer folikül sayı ve büyüklüğü üzerine kombine etkisi: dişi ratlarda in vivo çalışma

“…Previous findings demonstrated that EGCG has anti-proliferative effects 21,22 . Additionally, green tea also has an affinity for the ovaries and protective effects for the ovaries 10,11 .…”

Phytochemicals based chemopreventive and chemotherapeutic strategies and modern technologies to overcome limitations for better clinical applications

“…For the past 6-7 decades, chemotherapy has remained an effective anticancer strategy that targets proliferating cells. Chemotherapeutic drugs kill cancer cells via different and distinct mechanisms such as DNA damage, oxidative stress, cell cycle arrest, and cytoskeleton damage (Annovazzi, Mellai, & Schiffer, 2017;Belayachi et al, 2017;Farhan et al, 2016;Goldstein & Kastan, 2015;Pereira et al, 2017). Induction of apoptosis, necrosis, or necroptosis plays a determining role in chemotherapeutic agents-mediated cell death.…”