Selective Cytotoxic Action and DNA Damage by Calcitriol-Cu(II) Interaction: Putative Mechanism of Cancer Prevention

• DOI: 10.1371/journal.pone.0076191
• Publication Date: 2013-09-27T21:09:52Z
• Authors: Asim Rizvi; S. Saif Hasan; Imrana Naseem
• Keywords: Buthionine sulfoximine; Mechanism of Action

BackgroundVitamin D is known to play an important role in cancer-prevention. One of the features associated with onset malignancy elevation Cu (II) levels. The mode cancer-prevention mediated by calcitriol, biologically active form vitamin D, remain largely unknown. MethodsUsing exogenously added stimulate a like condition novel cellular system rabbit calcitriol overloaded lymphocytes, we assessed lipid peroxidation, protein carbonylation, DNA damage and consequent apoptosis. Free radical mediators were identified using free scavengers reaction was elucidated chelators redox metal ions. ResultsLipid peroxidation carbonylation (markers oxidative stress), fragmentation apoptosis observed due calcitriol-Cu interaction. Hydroxyl radicals, hydrogen peroxide superoxide anions mediate stress produced during this Amongst metals, copper found be responsible for reaction. ConclusionThis first report implicating interaction as cause selective cytotoxic action against malignant cells. We show that leads production fragmentation, which A putative mechanism presented explain biological effect.