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Advanced Pharmaceutical Bulletin
ISSN: 2228-5881      eISSN: 2251-7308  
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Article History
Submitted: 15 Aug 2013
Revised: 07 Oct 2013
First published online: 24 Dec 2013

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Adv Pharm Bull. 2014;4(2):185-189 doi: 10.5681/apb.2014.027
PMID:24511483        PMCID:PMC3915819

ABT-737, Synergistically Enhances Daunorubicin-Mediated Apoptosis in Acute Myeloid Leukemia Cell Lines

Original Research

Hassan Dariushnejad 1, Nosratallah Zarghami 1,2 * , Mohammad Rahmati 1,2, Samaneh Ghasemali 1, Zohreh Sadeghi 1, Zahra Davoudi 1, Hossein Jafari Tekab 3, Masoud Gandomkar Ghalhar 1

1 Department of Medical Biotechnology, Faculty of Advance Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.



Abstract
Purpose: 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. Conclusion: 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.





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