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

Dafna Rocker, Amkam Ravid, Uri A. Liberman, Osnath Garach-Jehoshua, Ruth Koren

Research output: Contribution to journalArticlepeer-review

Abstract

We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the cytotoxic action of TNF on MCF-7 human breast cancer cells and on adult bovine aortic endothelial cells. 1,25(OH)2D3 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)2D3 was specific, dose-dependent and apparent at a physiological concentration (0.1 nM) of the hormone. The potentiating effect of 1,25(OH)2D3 on TNF action was abolished by cycloheximide indicating that their interaction requires protein synthesis. Addition of 1,25(OH)2D3 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)2D3 may be due to an increase in the anti-cancer activity of the immune system.

Original languageEnglish
Pages (from-to)157-162
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume106
Issue number1-2
DOIs
StatePublished - Dec 1994

Keywords

  • Breast cancer (human)
  • Calcitriol
  • Endothelium
  • Tumor necrosis factor
  • Vitamin D

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