Vitamin D sensitizes breast cancer cells to the action of H2O2: mitochondria as a convergence point in the death pathway.
Calcitriol, the hormonal form of vitamin D3, sensitizes breast cancer cells to reactive oxygen species (ROS)-dependent cytotoxicity induced by various anticancer modalities. This effect could be due to increased generation of ROS and/ or to increased sensitivity of the target cells to ROS. This work examined the effect of calcitriol on the damage inflicted on breast cancer cells by the direct action of ROS represented by H2O2. Treatment of MCF-7 cells with H2O2 resulted in activation of caspase 7 as well as induction of caspase-independent cell death. Both were enhanced by 48-72 h of pretreatment with calcitriol. This effect was not due to modulation of H2O2 degradation or to a specific effect on *OH-mediated cytotoxicity. The H2O2-induced drop in mitochondrial membrane potential and release of cytochrome c were enhanced by calcitriol. These findings indicate that calcitriol sensitizes breast cancer cells to ROS-induced death by affecting event(s) common to both caspase-dependent and -independent modes of cell death upstream to mitochondrial damage.
Weitsman
Gregory E
GE
Basil and Gerald Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva 49100, Israel.
Koren
Ruth
R
Zuck
Efrat
E
Rotem
Carmela
C
Liberman
Uri A
UA
Ravid
Amiram
A
D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D002117:Calcitriol / Q000737:chemistry / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species; D013997:Time Factors; D014807:Vitamin D / Q000494:pharmacology*
D016877:Oxidants; D017382:Reactive Oxygen Species; D014807:Vitamin D; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D002117:Calcitriol