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Calcitriol‐induced DNA damage: Toward a molecular mechanism of selective cell death
Author(s) -
Hasan S. Saif,
Rizvi Asim,
Naseem Imrana
Publication year - 2013
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1199
Subject(s) - calcitriol , calcitriol receptor , chemistry , dna , dna damage , receptor , programmed cell death , vitamin d and neurology , mechanism (biology) , microbiology and biotechnology , cancer research , biochemistry , biology , endocrinology , apoptosis , philosophy , epistemology
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. © 2013 IUBMB Life, 65(9):787–792, 2013