Calcitriol-induced DNA damage: toward a molecular mechanism of selective cell death.

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TitleCalcitriol-induced DNA damage: toward a molecular mechanism of selective cell death.
Publication TypeJournal Article
Year of Publication2013
AuthorsS Hasan, S, Rizvi, A, Naseem, I
JournalIUBMB Life
Volume65
Issue9
Pagination787-92
Date Published2013 Sep
ISSN1521-6551
KeywordsAnimals, Antineoplastic Agents, Apoptosis, Calcitriol, DNA, DNA Damage, Humans, Models, Molecular, Neoplasms, Nucleic Acid Conformation, Protein Binding, Protein Structure, Tertiary, Receptors, Calcitriol
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.

DOI10.1002/iub.1199
Alternate JournalIUBMB Life
PubMed ID23913678