Calcitriol and lexicalcitol (KH1060) inhibit the growth of human breast adenocarcinoma cells by enhancing transforming growth factor-beta production.
The mechanisms involved in the antiproliferative action of calcitriol (1 alpha, 25(OH)2D3) were investigated using human breast carcinoma epithelial cells (the MCF-7 cell line). Calcitriol and KH1060, a synthetic analog, inhibited cell growth in a time-and dose-dependent way. The substances similarly stimulated total TGF-beta secretion after 24 hours, and Northern blot analyses showed that mRNA levels for TGF-beta 1 were increased, as well. When MCF-7 cells were co-incubated with calcitriol and a neutralizing anti TGF-beta 1, beta 2, beta 3 antibody, growth inhibition was completely abrogated. With KH1060, the antibody could only partly block growth inhibition. This study shows that TGF-beta is involved in the growth response to calcitriol and KH1060 in MCF-7 cells.
Mercier
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Laboratoire de Nutrition et Sécurité Alimentaire, INRA-CRJ, Jouy en Josas, France.
Chaumontet
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Gaillard-Sanchez
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Martel
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Heberden
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C
D000230:Adenocarcinoma / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; C074279:KH 1060; D002117:Calcitriol