title: ABT-737, Synergistically Enhances Daunorubicin-Mediated Apoptosis in Acute Myeloid Leukemia Cell Lines.
abstract: OBJECTIVE
  Intensive chemotherapy with daunorubicin (DNR) is associated with serious side effects in acute myeloid leukemia (AML) patients. In this study the effect of small-molecule BH3-mimetic, ABT-737, on the sensitivity of HL60 and U937 AML cell lines was investigated.
  
  
  METHODS
  The cytotoxic effects of DNR and ABT-737, alone or in combination were assessed using MTT assay and combination index analysis. The effects of treatments on the cell proliferation was determined by trypan blue assay. ELISA cell death assay was used for measurement of apoptosis.
  
  
  RESULTS
  IC50 values of DNR and ABT-737 were 2.52 and 0.59 µM for HL-60 cells line and 1.31 and 0.80 µM for U937 cell line at 24 h, respectively. Surprisingly, combination treatment significantly lowered the IC50 values in a synergic manner in both cell lines. Moreover, treatment with a mixture of two agents had more growth inhibition effect relative to the monotherapy. RESULTS of apoptosis assay showed that the cytotoxic effects are related to the enhancement of apoptosis.
  
  
  CONCLUSIONS
  Our study suggests that ABT-737 synergistically enhances the cytotoxic effect of DNR in AML cell lines and therefore may be useful to overcome chemoresistance of leukemia patients.
authors: Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Hassan
authors: H
authors: Dariushnejad
authors: Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. ; Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Nosratallah
authors: N
authors: Zarghami
authors: Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. ; Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Mohammad
authors: M
authors: Rahmati
authors: Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Samaneh
authors: S
authors: Ghasemali
authors: Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Zohreh
authors: Z
authors: Sadeghi
authors: Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Zahra
authors: Z
authors: Davoodi
authors: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Hossein
authors: H
authors: Jafari Tekab
authors: Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Masoud
authors: M
authors: Gandomkar Ghalhar
keywords: ABT-737; Acute myeloid leukemia; Apoptosis; Combination; Daunorubicin