Bosutinib Reduces the Efficacy of Dasatinib in Triple-negative Breast Cancer Cell Lines

Background: Triple-negative breast cancer (TNBC) is an aggressive sub-type of breast cancer. Dasatinib and bosutinib are FDA-approved Src/Abl kinase inhibitor drugs. Dasatinib potently inhibits the proliferation of many TNBC cell lines. Materials and Methods: The cell viability/proliferation for a panel of 4 TNBC cell lines was measured by detection of cellular ATP levels and cell numbers were directly determined by automated cell counting. Results: Bosutinib (<= 1 mu M) had little to no inhibitory activity on cell viability/proliferation, while dasatinib-alone generated potent IC50 values of <100 nM. Combination treatment of cells with both dasatinib and bosutinib resulted in reduced efficacy of dasatinib in all four cell lines, with two of them displaying a dramatic loss of efficacy. Direct cell counting confirmed that bosutinib enhanced cell proliferation in the presence of dasatinib. Conclusion: Bosutinib potently reduced the in vitro anti-proliferative efficacy of dasatinib in TNBC cell lines. We, hereby, report on a novel drug-induced loss in dasatinib sensitivity.