Combined effects of 13-cis-retinoic acid, tamoxifen and interferon on the growth of human breast cancer cells

We studied the effect of 13-cis-retinoic acid (13-cRA) alone and in combination with interferons (IFNs) and tamoxifen (TAM) in two established human breast cancer cell lines: the estrogen-sensitive CG-5 and the estrogen-insensitive MDA-MB-453 cells. 13-cRA (10(-9)-10(-5) M) significantly reduced the growth of both cell lines in a dose-dependent fashion, after 3 and 6 days of treatment. When the retinoid (10(-9)-10(-5) M) was combined with natural beta-IFN (100-1000 IU/ml) for 6 days, we observed a growth inhibition more pronounced than that produced by each of the two single agents in both CG-5 and MDA-MB-453 cells. Only in the former model was the inhibitory effect synergistic at all the drug concentrations used. Association of 13-cRA (10(-9)-10(-5) M) and recombinant alpha2a-IFN (100-1000 IU/ml) or TAM (10(-7)-10(-6) M) did not determine an additive or synergistic effect on the growth of CG-5 cells.