Vitamin D enhances caspase-dependent and independent TNF-induced breast cancer cell death: the role of reactive oxygen species.
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.
Weitsman
G E
GE
Felsenstein Medical Research Center, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ravid
A
A
Liberman
U A
UA
Koren
R
R
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002117:Calcitriol / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases; D002117:Calcitriol