In this study, we show that Anaphase Promoting Complex (APC) activity is low in multiple-drug-resistant (MDR) MCF7 breast cancer cells and that activation of the APC using the small chemical APC activator M2I-1 restores APC activity in resistant cells, recouples cell cycle progression with APC substrate degradation, and re-sensitizes MCF7 cells selected for resistance to tamoxifen (MCF7TAM) or DOX (MCF7DOX) to levels noted in unmodified parental cell lines. This evidence concerns the gene APC and breast carcinoma.