title: Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma.
abstract: Calcitriol is the metabolically active form of Vitamin D and is known to kill cancer cells. Using the rat model of DEN induced hepatocellular carcinoma we show that there is a marked increase in cellular levels of copper in hepatocellular carcinoma and that calcitriol-copper interaction leads to reactive oxygen species mediated DNA breakage selectively in hepatocellular carcinoma cells. In vivo studies show that calcitriol selectively induces severe fluctuations in cellular enzymatic and non enzymatic scavengers of reactive oxygen species in the malignant tissue. Lipid peroxidation, a well established marker of oxidative stress, was found to increase, and substantial cellular DNA breakage was observed. We propose that calcitriol is a proxidant in the cellular milieu of hepatocellular carcinoma cells, and this copper mediated prooxidant action of calcitriol causes selective DNA breakage in malignant cells, while sparing normal (non malignant) cells.
authors.affiliation: Section of Radiobiology, Department of Radiology, The Biomedical Research Tower, The Ohio State University, 460 W 12th Avenue, Columbus, OH, USA.|Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India.
authors.forename: Asim
authors.initials: A
authors.lastname: Rizvi
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Farhan
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India. imrananaseem2009@gmail.com.
authors.forename: Imrana
authors.initials: I
authors.lastname: Naseem
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India.
authors.forename: S M
authors.initials: SM
authors.lastname: Hadi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D002117:Calcitriol / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D003300:Copper / Q000378:metabolism*; D004249:DNA Damage; D006801:Humans; D015227:Lipid Peroxidation; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D003300:Copper; D002117:Calcitriol
keywords: Calcitriol; Cancer; Cell death; Copper; ROS