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Anticancer Res. 2014 Apr;34(4):1629-35.

Bosutinib reduces the efficacy of Dasatinib in triple-negative breast cancer cell lines.

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1
1801 Fayetteville St, BRITE Bldg, Rm 1019, North Carolina Central University, Durham, NC 27707, U.S.A. jscott@nccu.edu.

Abstract

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 μM) 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.

KEYWORDS:

Bosutinib; breast cancer; dasatinib

PMID:
24692691
PMCID:
PMC4128406
[Indexed for MEDLINE]
Free PMC Article
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