Breast Carcinoma Cell Targeted Therapy by Novel Vitamin D Analog.

Recently we have shown that 1-alpha OHD5, a novel vitamin D analog has both cell differentiating and growth inhibitory effects in selected human breast carcinoma cell lines. We observed enhanced expression of intracytoplasmic casein and lipid droplets, nm23 and ICAM-1 proteins following days in vitro treatment with 1-alpha OHD5. In the proposed study we further evaluated effect of this novel compounds on other biomarkers associated with breast cancer cell differentiation. We studied in vivo and in vitro effects of 1-alpha OHD5 on 4 different cell lines. 1-alpha OHD5 showed pronounced growth inhibitory effect in all ER breast carcinoma cells. It enhanced expression of alpha2 integrin, beta-1 integrin, and CK-8 proteins in breast cancer cells irrespective of their ER status. Changes in expression of later proteins was only observed in VDR cells. In vivo, 1-alpha ORD5 supplemented in diet inhibited growth of ZR-75-1 and UISO-BCA-4 cells. Our ultimate goal is to conjugate and link this vitamin D analog to Her-2neu antibody in order to specifically target breast cancer cells in women. We selected ZR-75-1 cells known to have overexpression of Her-2 receptor for further in vivo work. In vivo growth of ZR-75-1 cells was significantly reduced by Her-2 antibody treatment.