Differentiation of human breast carcinoma cells by a novel vitamin D analog: 1alpha-hydroxyvitamin D5.
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| Abstract |
The active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3, can induce differentiation in breast cancer cells; however, it is hypercalcemic in vivo. Therefore, development of non-calcemic analogs of vitamin D has received considerable attention. Recently, we synthesized an analog of vitamin D [1alpha(OH)D5] that exhibits much less calcemic activity than 1alpha,25-dihydroxyvitamin D3. In this study, we evaluated the cell-differentiating action of 1alpha(OH)D5 in breast cancer cells. Following 10 days treatment with 1alpha(OH)D5 [(10-7 M) in UISO-BCA-4], we observed induction of intracytoplasmic casein, intracytoplasmic lipid droplets, ICAM-1, nm23, and specific biomarkers associated with breast cell differentiation. 1alpha(OH)D5 treatment also showed induction of vitamin D receptor and TGFbeta1 proteins. UISO-BCA-4 cells pretreated for 10 days in vitro with 1 microM 1alpha(OH)D5 failed to form tumors when transplanted into athymic mice. Similarly, 4 and 8 ng 1alpha(OH)D5 treatment three times weekly inhibited the growth of UISO-BCA-4 cells injected into athymic mice. These results suggest that this new vitamin D analog may be of significant therapeutic value for breast cancer.
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| Authors | R R Mehta, L Bratescu, J M Graves, A Green, R G Mehta |
| Journal | International journal of oncology (Int J Oncol) Vol. 16 Issue 1 Pg. 65-73 (Jan 2000) ISSN: 1019-6439 [Print] Greece |
| PMID | 10601550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.) |
| Chemical References |
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