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.)
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Chemical References |
- 1-hydroxyvitamin D5
- Antineoplastic Agents
- Biomarkers
- Hydroxycholecalciferols
- Vitamin D
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Biomarkers
- Breast Neoplasms
- Cell Differentiation
(drug effects)
- Cell Division
(drug effects)
- Cell Size
(drug effects)
- Female
- Humans
- Hydroxycholecalciferols
(pharmacology, therapeutic use)
- Mammary Neoplasms, Experimental
(drug therapy)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
- Tumor Cells, Cultured
- Vitamin D
(analogs & derivatives, pharmacology)
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