1,24(S)-dihydroxyvitamin D2, an endogenous vitamin D2 metabolite, inhibits growth of breast cancer cells and tumors.

Abstract

BACKGROUND:

1,24-Dihydroxyvitamin D2 (1,24(OH)2D2) is a naturally occurring metabolite of vitamin D2 with low calcemic activity and potent antiproliferative activity. We evaluated the activity of 1,24(OH)2D2 in breast cancer models.

MATERIALS AND METHODS:

The antiproliferative activity of 1,24(OH)2D2 was quantitated against human and murine breast cancer cell lines. The antitumor activity of 1,24(OH)2D2 was quantitated using MCF-7 xenografts in nude mice.

RESULTS:

1,24(OH)2D2 inhibited growth of vitamin D receptor (VDR)-positive, but not VDR-negative, breast cancer cells. 1,24(OH)2D2 (10 microg/kg or 50 microg/kg) reduced MCF-7 xenograft growth by 50% after five weeks. Tumor morphology in treated animals was consistent with replacement of epithelial cells by stromal tissue. Mice treated with 1,24(OH)2D2 showed no loss of body weight, hypercalcemia or kidney calcification.

CONCLUSION:

1,24(OH)2D2 inhibits growth of breast cancer cells via VDR-dependent mechanisms; its complete lack of toxicity and significant antitumor activity supports further development for chemotherapeutic applications.

• Authors: Glendon M Zinser, Emily Tribble, Meggan Valrance, Colleen M Urben, Joyce C Knutson, Richard B Mazess, Stephen A Strugnell, Joellen Welsh
• Journal: Anticancer research (Anticancer Res) 2005 Jan-Feb Vol. 25 Issue 1A Pg. 235-41 ISSN: 0250-7005 [Print] Greece
• PMID: 15816543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ergocalciferols
• Receptors, Calcitriol
• dihydroxy-vitamin D3
• 1,24-dihydroxyvitamin D2
• Vitamin D
• Calcium

Topics

• Animals
• Body Weight (drug effects)
• Breast Neoplasms (blood, drug therapy, pathology)
• Calcium (blood)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Ergocalciferols (blood, pharmacology)
• Female
• Humans
• Kidney (drug effects, pathology)
• Mice
• Mice, Nude
• Receptors, Calcitriol (metabolism)
• Vitamin D (analogs & derivatives, pharmacology)
• Xenograft Model Antitumor Assays