Novel therapeutic approach: organic arsenical (melarsoprol) alone or with all-trans-retinoic acid markedly inhibit growth of human breast and prostate cancer cells in vitro and in vivo

The organic arsenical known as melarsoprol (Mel-B) is used to treat African trypanosomiasis. Recently, another arsenical, As2O3 was shown to be effect ive in treatment of acute promyelocytic leukaemia. We have investigated the anti-tumour activities of Mel-B either with or without all-trans-retinoic acid (ATRA) using the MCF-7 human breast cancer cells, as well as the PC-3 and DU 145 human prostate cancer cells both in vitro and in vivo. The antip roliferative effects of Mel-B and/or ATRA against breast and prostate cance r were tested in vitro using clonogenic assays and in vivo in triple immuno deficient mice. Furthermore, the mechanism of action of these compounds was studied by examining the cell cycle, levels of bcl-2, apoptosis and antipr oliferative potency using a pulse-exposure assay. Clonogenic assays showed ;hat the cancer cell lines were sensitive to the inhibitory effect of Mel-B (effective dose that inhibited 50% clonal growth [ED50]: 7 x 10(-9) M for MCF-7, 2 x 10(-7) an for PG3, 3 x 10(-7) M for DU145 cells; Remarkably, the combination of Mel-B and ATRA had an enhanced antiproliferative activity a gainst all three cancer cell lines. Furthermore; the combination of Mel-8 a nd ATRA induced a high level of apoptosis in all three cell lines. Treatmen t of PC-3 and MCF-7 tumours growing in triple immun,deficient mice with Mel -B and ATRA either atone or in combination markedly retarded tumour size an d weight of the tumours without major side-effects. In conclusion, our resu lts suggest that either Mel-B alone or with ATRA may be a useful, novel the rapy for breast and prostate cancers. (C) 2000 Cancer Research Campaign.