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


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.


CONCLUSIONS
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.
Zinser
Glendon M
GM
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Tribble
Emily
E
Valrance
Meggan
M
Urben
Colleen M
CM
Knutson
Joyce C
JC
Mazess
Richard B
RB
Strugnell
Stephen A
SA
Welsh
Joellen
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000097:blood; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004872:Ergocalciferols / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D018167:Receptors, Calcitriol / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; C063087:1,24-dihydroxyvitamin D2; D014807:Vitamin D; D002118:Calcium