Cu(II)-vitamin D interaction leads to free radical-mediated cellular DNA damage: a novel putative mechanism for its selective cytotoxic action against malignant cells.
Vitamin D (vit D) is a known anticancer molecule, and cancer cells are reported to have elevated levels of Cu(II) ions. In this study, we show that interaction of vit D and Cu(II) leads to the formation of hydroxyl free radicals, superoxide anion and hydrogen peroxide, which causes severe oxidative stress, selectively in malignant cells. We show that the production of these reactive oxygen species causes cellular DNA fragmentation which may cause cell death. A novel putative chemical mechanism explaining how vit D causes cell death by DNA damage, selectively in malignant cells, is proposed.
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P., 202002, India.
Asim
A
Rizvi
Sandesh
S
Chibber
Imrana
I
Naseem
D002413:Cations, Divalent / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology*
D002413:Cations, Divalent; D002614:Chelating Agents; D005609:Free Radicals; D017382:Reactive Oxygen Species; D014807:Vitamin D; D003300:Copper; D004247:DNA; D006861:Hydrogen Peroxide