title: Bosutinib reduces the efficacy of Dasatinib in triple-negative breast cancer cell lines.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1801 Fayetteville St, BRITE Bldg, Rm 1019, North Carolina Central University, Durham, NC 27707, U.S.A. jscott@nccu.edu.
authors.forename: Mike
authors.initials: M
authors.lastname: Tarpley
authors.forename: Temesgen T
authors.initials: TT
authors.lastname: Abdissa
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johnson
authors.forename: John E
authors.initials: JE
authors.lastname: Scott
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000069439:Dasatinib; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009570:Nitriles / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011804:Quinolines; D013844:Thiazoles; C471992:bosutinib; D000069439:Dasatinib
keywords: Bosutinib; breast cancer; dasatinib