|Title||Calcitriol-induced DNA damage: toward a molecular mechanism of selective cell death.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||S Hasan, S, Rizvi, A, Naseem, I|
|Date Published||2013 Sep|
|Keywords||Animals, Antineoplastic Agents, Apoptosis, Calcitriol, DNA, DNA Damage, Humans, Models, Molecular, Neoplasms, Nucleic Acid Conformation, Protein Binding, Protein Structure, Tertiary, Receptors, Calcitriol|
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.
|Alternate Journal||IUBMB Life|