TY - JOUR
T1 - 1,25-Dihydroxyvitamin d3 potentiates the cytotoxic effect of TNF on human breast cancer cells
AU - Rocker, Dafna
AU - Ravid, Amkam
AU - Liberman, Uri A.
AU - Garach-Jehoshua, Osnath
AU - Koren, Ruth
N1 - Funding Information:
This work forms part of the Ph.D. Thesis presentedb y Ms. Dafna Rocker to the Sackler Faculty of Medicine, Tel Aviv University. This research was supported by the Chuma Munka Averbuch Memorial Fund via the Israel Cancer Association and by The Israel Science Foundation administeredb y The Israel Academy of Sciences and Humanities (researchg rant no. 684/931) and by Tel Aviv University Basic Science Research Fund. Thanks are due to Ms. Einat Beeri for her helpful assistanced uring the selection of the TNF sensitive subline of MCF-7 cells.
PY - 1994/12
Y1 - 1994/12
N2 - 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.
AB - 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.
KW - Breast cancer (human)
KW - Calcitriol
KW - Endothelium
KW - Tumor necrosis factor
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=0028670468&partnerID=8YFLogxK
U2 - 10.1016/0303-7207(94)90198-8
DO - 10.1016/0303-7207(94)90198-8
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AN - SCOPUS:0028670468
SN - 0303-7207
VL - 106
SP - 157
EP - 162
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -