Weitsman G E, Ravid A, Liberman U A, Koren R
Felsenstein Medical Research Center, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ann N Y Acad Sci. 2003 Dec;1010:437-40. doi: 10.1196/annals.1299.079.
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.
骨化三醇，即维生素D的激素形式，增强了肿瘤坏死因子（TNF）诱导的MCF-7乳腺癌细胞的细胞毒性。在存在泛半胱天冬酶抑制剂的情况下，它增加了半胱天冬酶-3样活性的诱导以及TNF诱导的不依赖半胱天冬酶的细胞毒性。抗氧化剂N-乙酰半胱氨酸、谷胱甘肽、硫辛酸和抗坏血酸显著降低了该激素对TNF诱导的半胱天冬酶激活的作用，证明活性氧（ROS）参与了该激素与细胞因子之间的相互作用。通过荧光探针JC-1评估，骨化三醇增强了TNF诱导的线粒体膜电位下降。我们推测，TNF与骨化三醇在线粒体水平上的相互作用是TNF诱导的、ROS介导的依赖和不依赖半胱天冬酶的细胞死亡增强的基础。
