Combination therapy of a vitamin D3 analog and all-trans-retinoic acid:: Effect on human breast cancer in nude mice

Background: Vitamin D-3 analogs and all-trans-retinoic acid (ATRA) are able to inhibit the growth of a variety of malignant cells. Material and Methods: We examined the ability of three vitamin D-3 analogs to inhibit the growth of a human mammary cancer cell line (MCF-7) in Beige Nude rid (BNX) mice either alone or with ATRA. Vitamin D-3 analogs 1,25 dihydroxyvitamin D-3 (code name, compound C), 1,25(OH)(2)-16-ene-23-yne-19-nor-26,27-F-6-D-3 (compound LH) and 24a,26a,27a,-trihomo-22,24-diene-1,25(OH)(2)D-3 (EB1089) were used Results: The antitumor effect of ATRA alone was greater than that of either of the vitainin D-3 analogs alone, and an additive effect was observed when a vitamin D-3 analog ann ATRA were administered together EB1089 was the most potent vitamin D-3 analog; and EB1089 pku A TRA was the most potent combination decreasing the tumor mass nearly 3-fold compared to tumors of diluent control mice. None of the animals became hypercalcemic. Their complete blood counts, serum electrolyte analysis as well as their liver and renal functions were all fairly similar and within the normal range. Conclusion: This combination of a vitamin D-3 analog and ATRA has the potential to be an adjuvant therapy for breast cancer.