Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions

Abstract

Turmeric spice contains curcuminoids, which are polyphenolic compounds found in the Curcuma longa plant’s rhizome. This class of molecules includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Using prostate cancer cell lines PC3, LNCaP, DU145, and C42B, we show that curcuminoids inhibit cell proliferation (measured by MTT assay) and induce apoptosis-like cell death (measured by DNA/histone ELISA). A copper chelator (neocuproine) and reactive oxygen species scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide) significantly inhibit this reaction, thus demonstrating that intracellular copper reacts with curcuminoids in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitize normal breast epithelial cells (MCF-10A) to curcumin-mediated growth inhibition, as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters CTR1 and ATP7A in MCF-10A cells, which is attenuated by the addition of curcumin in the medium. We propose that the copper-mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of curcuminoids.