title: Calcitriol-induced DNA damage: toward a molecular mechanism of selective cell death.
abstract: Calcitriol, the biologically active form of vitamin D, is known to function as an important anticancer agent. The exact mechanism by which calcitriol exerts its effects remains unknown. Recent evidence suggests a link between calcitriol-induced, free-radical-mediated DNA damage and cell death, in the presence of elevated levels of copper, such as those observed in malignant cells. As calcitriol is a lipid-soluble molecule, its interaction with DNA and copper would require a "chaperone"-like molecule, which binds the relatively hydrophobic calcitriol and polar DNA. A candidate protein is the vitamin D receptor (VDR), which binds both molecules. Using the recently elucidated full-length structure of the VDR molecule, we present and discuss three possible mechanisms to explain the interaction between calcitriol and DNA, as mediated by VDR.
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, Purdue University, West Lafayette, IN, USA.
authors.forename: S Saif
authors.initials: SS
authors.lastname: Hasan
authors.forename: Asim
authors.initials: A
authors.lastname: Rizvi
authors.forename: Imrana
authors.initials: I
authors.lastname: Naseem
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002117:Calcitriol / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004249:DNA Damage; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D004247:DNA; D002117:Calcitriol
keywords: antioxidants; apoptosis; cell death; reactive oxygen species; structural biology