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Vitamin D Enhances Caspase‐Dependent and Independent TNF‐Induced Breast Cancer Cell Death
Author(s) -
WEITSMAN GE,
RAVID A,
LIBERMAN UA,
KOREN R
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.079
Subject(s) - calcitriol , ascorbic acid , chemistry , reactive oxygen species , tumor necrosis factor alpha , apoptosis , caspase , programmed cell death , cytotoxicity , glutathione , vitamin e , cancer research , mitochondrion , caspase 3 , endocrinology , pharmacology , medicine , vitamin d and neurology , biochemistry , biology , antioxidant , in vitro , enzyme , food science
A bstract : 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.