1,25-Dihydroxyvitamin d3 potentiates the cytotoxic effect of TNF on human breast cancer cells

Abstract We studied the effect of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) on the cytotoxic action of TNF on MCF-7 human breast cancer cells and on adult bovine aortic endothelial cells. 1,25(OH) 2 D 3 increased the effect of TNF on MCF-7 cells but not on endothelial cells over a wide TNF concentration range. At a suboptimal concentration (1 ng/ml) the potentiation was twofold. The effect of 1,25(OH) 2 D 3 was specific, dose-dependent and apparent at a physiological concentration (0.1 nM) of the hormone. The potentiating effect of 1,25(OH) 2 D 3 on TNF action was abolished by cycloheximide indicating that their interaction requires protein synthesis. Addition of 1,25(OH) 2 D 3 13 h after TNF in a 28-h assay was sufficient to induce its full potentiating effect indicating that the hormone modulates a late event in the cytokine's action. These data suggest that some of the in vivo antitumor effects of 1,25(OH) 2 D 3 may be due to an increase in the anti-cancer activity of the immune system.