1α,25-Dihydroxyvitamin D3 inhibits cell growth and NFκB signaling in tamoxifen-resistant breast cancer cells

• Resistance to antiestrogens is a major clinical problem in current breast cancer treatment and development of new treatment strategies for these tumors is highly prioritized. In this study, we have investigated the effects of 1 alpha,25-dihydroxyvitamin D-3 on the proliferation of tamoxifen-resistant cells. Further, we have investigated on a molecular level the effects of vitamin D on NF kappa B signaling in tamoxifen-resistant breast cancer cells. Parental human breast cancer MCF-7 cells and four tamoxifen-resistant sublines have been used to investigate the effects of 1 alpha,25-dihydroxyvitamin 133 on cell proliferation using a colorimetric method, gene expression using quantitative PCR, protein phosphorylation using Western blot analysis and cellular localization of proteins using immunofluorescence microscopy. We found that 1 alpha,25-dihydroxyvitamin D-3 is able to strongly decrease the growth of both tamoxifen-sensitive and -resistant breast cancer cells and that this antiproliferative effect of 1 alpha,25-dihydroxyvitamin D-3 might be mediated via inhibition of the NF kappa B pathway. We found that 1 alpha,25-dihydroxyvitamin D-3 stimulates the gene expression of IkB, an NM-inhibiting protein, and that cells pretreated with 1 alpha,25-dihydroxyvitamin D-3 have a decreased sensitivity to TNF alpha stimulation. Further, we show that 1 alpha,25-dihydroxyvitamin D-3 treatment strongly decreases the TNF alpha-induced translocation of p65 into the nucleus. This manuscript reports novel findings regarding the effects of 1 alpha,25-dihydroxyvitamin D-3 on NF kappa B signaling in tamoxifen-resistant breast cancer cells and suggests that vitamin D might be interesting for further evaluation as a new strategy to treat antiestrogen-resistant breast cancers. (C) 2014 Elsevier Inc. All rights reserved.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

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