Annals of the New York Academy of Sciences · 2003 · 44 citations · 2 references
Life SciencesCell BiologyOncologyApoptosisCellular MetabolismMitochondrial BiologyApoptosis In CancerApoptotic SignalingCaspase ActivationMitochondrial DysfunctionReactive Oxygen SpeciesVitamin DAntioxidantsCaspase-mediated ApoptosisMitochondrial Apoptotic SignalingMitochondrial Cell Death PathwaysMitochondrial Membrane Potential CollapseMitochondrial Pathway Of ApoptosisMitochondrial PathwaysReactive Oxygen Species Generation
Calcitriol, the hormonal form of vitamin D, enhanced TNF-induced cytotoxicity in MCF-7 breast cancer cells. It increased the induction of caspase-3-like activity and TNF-induced caspase-independent cytotoxicity in the presence of a pan-caspase inhibitor. The antioxidants N-acetylcysteine, glutathione, lipoic acid, and ascorbic acid markedly reduced the effect of the hormone on TNF-induced caspase activation, attesting to the involvement of reactive oxygen species (ROS) in the cross-talk between the hormone and the cytokine. Calcitriol augmented the drop in mitochondrial membrane potential induced by TNF as assessed by the fluorescent probe JC-1. We postulate that the interaction of TNF and calcitriol on the level of the mitochondria underlies the enhancement of TNF-induced, ROS-mediated caspase-dependent and -independent cell death.
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