Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species
- 6 December 2010
- journal article
- research article
- Published by Wiley in Molecular Nutrition & Food Research
- Vol. 55 (4), 553-559
- https://doi.org/10.1002/mnfr.201000329
Abstract
Scope: Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high isoflavone intake through soy consumption have lower rates of breast, prostate, and colon cancer. Isoflavone genistein in soybean is considered a potent chemopreventive agent against cancer. Although several mechanisms have been proposed, a clear anticancer action mechanism of genistein is still not known. Methods and results: Here, we show that the cytotoxic action of genistein against breast cancer cells involves mobilization of endogenous copper. Further, whereas the copper specific chelator neocuproine is able to inhibit the apoptotic potential of genistein, the molecules which specifically bind iron (desferroxamine mesylate) and zinc (histidine) are relatively ineffective in causing such inhibition. Also, genistein‐induced apoptosis in these cells is inhibited by scavengers of reactive oxygen species (ROS) implicating ROS as effector elements leading to cell death. Conclusions: As copper levels are known to be considerably elevated in almost all types of cancers, in this proof‐of‐concept study we show that genistein is able to target endogenous copper leading to prooxidant signaling and consequent cell death. We believe that such a mechanism explains the anticancer effect of genistein as also its preferential cytotoxicity towards cancer cells.Keywords
Funding Information
- UGC and CSIR, New Delhi
This publication has 27 references indexed in Scilit:
- Apoptosis‐inducing effect of garcinol is mediated by NF‐κB signaling in breast cancer cellsJournal of Cellular Biochemistry, 2010
- Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin AMolecular Nutrition & Food Research, 2009
- Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell lineCancer Letters, 2009
- Elevated copper and oxidative stress in cancer cells as a target for cancer treatmentCancer Treatment Reviews, 2009
- Multi-targeted therapy of cancer by genisteinCancer Letters, 2008
- Polyphenols Are Intensively Metabolized in the Human Gastrointestinal Tract after Apple Juice ConsumptionJournal of Agricultural and Food Chemistry, 2007
- DNA damage induced by resveratrol and its synthetic analogues in the presence of Cu (II) ions: Mechanism and structure-activity relationshipFree Radical Biology & Medicine, 2006
- A threshold concept for cancer therapyMedical Hypotheses, 2000
- Green Tea Constituent Epigallocatechin-3-Gallate and Induction of Apoptosis and Cell Cycle Arrest in Human Carcinoma CellsJNCI Journal of the National Cancer Institute, 1997
- Quantitative analysis of copper, zinc and copper/zinc ratio in selected human brain tumorsJournal of Neuro-Oncology, 1993