Tumor Biology

, Volume 36, Issue 5, pp 3661–3668 | Cite as

Calcitriol induced redox imbalance and DNA breakage in cells sharing a common metabolic feature of malignancies: Interaction with cellular copper (II) ions leads to the production of reactive oxygen species

Research Article

Abstract

Calcitriol is known to selectively kill malignant cells, however, not much is known about the mechanism by which it kills malignant cells and spares the “normal” cells. Since elevation of cellular copper is a metabolic condition common to all malignancies, we developed a mouse model to mimic this condition and treated the animals with calcitriol. It was observed that calcitriol–copper interaction in vivo causes severe fluctuations in cellular enzymatic and nonenzymatic scavengers of reactive oxygen species (ROS). Lipid peroxidation, a well-established marker of oxidative stress, was found to increase, and a substantial cellular DNA breakage was observed. Calcitriol–copper interaction in vivo was observed to lead the cells to an apoptosis like cell death. We propose that the interaction of calcitriol and copper within malignant cells and the consequent redox scavenger fluctuations and ROS-mediated DNA breakage may be one of the several mechanisms by which calcitriol causes selective cell death of malignant cells, while sparing normal cells.

Keywords

Cancer Calcitriol Copper Cell death ROS 

Abbreviations

ANOVA

Analysis of variance

ROS

Reactive oxygen species

SEM

Standard error of mean

TBARS

Thiobarbituric acid reactive substances

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of Life SciencesAligarh Muslim UniversityAligarhIndia
  2. 2.Section of Radiobiology, Department of Radiology, The Biomedical Research TowerThe Ohio State UniversityColumbusUSA
  3. 3.Department of PathologyGovernment Medical CollegeHaldwaniIndia

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