Carcinogenesis Advance Access published online on September 29, 2005
Carcinogenesis, doi:10.1093/carcin/bgi231
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1 Department of Surgical Oncology, University of Illinois at Chicago, Chicago, IL 60612; Department of Human Nutrition, University of Illinois at Chicago, Chicago, IL 60612
* To whom correspondence should be addressed. Several studies have established the active form of vitamin D3 as an effective tumor-suppressing agent; however, its anti-tumor activity is achieved at doses that are hypercalcemic in vivo. Therefore, less calcemic vitamin D3 analog, 1
Received April 27, 2005
Revised September 13, 2005
Accepted September 17, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Growth inhibition of carcinogen-transformed MCF-12F breast epithelial cells and hormone-sensitive BT-474 breast cancer cells by 1
-hydroxyvitamin D5
2 IIT Research Institute, Illinois Institute of Technology, Chicago, IL 60616
3 Department of Surgical Oncology, University of Illinois at Chicago, Chicago, IL 60612
4 Department of Surgical Oncology, University of Illinois at Chicago, Chicago, IL 60612; Department of Human Nutrition, University of Illinois at Chicago, Chicago, IL 60612; IIT Research Institute, Illinois Institute of Technology, Chicago, IL 60616
Rajendra G. Mehta, E-mail: RMehta{at}iitri.org
Abstract 
-hydroxy-24-ethyl-cholecalciferol (1[OH]D5), was evaluated for its potential use in breast cancer chemoprevention. Previously, 1(OH)D5 showed anti-carcinogenic activity in several in vivo and in vitro models. However, its effects on growth of normal tissue were not known. The present study was conducted to determine the effects of 1(OH)D5 on the growth of normal mouse mammary gland and normal-like human breast epithelial MCF-12F cells and to compare these effects with carcinogen-transformed MCF-12F and breast cancer cells. No significant difference was observed in the growth or morphology of cultured mouse mammary glands and MCF-12F cells in presence of 1(OH)D5. However, the transformed MCF-12F cells underwent growth inhibition (40-60%, p < 0.05) upon 1(OH)D5 treatment as determined by cell viability assays. Cell cycle analysis showed marked increase (50%) in G-1 phase in cells treated with 1(OH)D5 compared to the controls. Moreover, the percentage of cells in the synthesis (S) phase of cell cycle was decreased by 70% in transformed MCF-12F, BT-474, and MCF-7 cells. The growth arrest was preceded by increase in expression of cell cycle regulatory proteins p21Waf-1 and p27Kip-1. In addition, differential expression studies of parent and transformed MCF-12F cell lines using microarrays showed that prohibitin was increased four-fold in the transformed cells. These results indicate that the growth inhibitory effect of 1(OH)D5 was achieved in both carcinogen-transformed MCF12F and breast cancer cells at a dose that was non-inhibitory in normal-like breast epithelial cells.
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