Combination therapy of a vitamin D-3 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 Method s: We examined the ability of three vitamin D-3 analogs to inhibit the grow th 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 (com pound 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 observ ed 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 pote nt combination decreasing the tumor mass nearly 3-fold compared to tumors o f diluent control mice. None of the animals became hypercalcemic. Their com plete blood counts, serum electrolyte analysis as well as their liver and r enal functions were all fairly similar and within the normal range. Conclus ion: This combination of a vitamin D-3 analog and ATRA has the potential to be an adjuvant therapy for breast cancer.