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:: Volume 4, Issue 2 (Int J Mol Cell Med 2015) ::
Int J Mol Cell Med 2015, 4(2): 94-102 Back to browse issues page
Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation
Ahmad Fatemi1, Ahmad Kazemi1, Meysam Kashiri1, Majid Safa 2
1- Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
2- Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. , safa.m@iums.ac.ir
Abstract:   (6129 Views)
Recognition of the molecular mechanisms of cAMP action against DNA damage-induced apoptosis can be useful to improve the efficacy of DNA damaging therapeutic agents. Considering the critical role of bcl-2-associated death promoter (BAD) and p53 proteins in DNA damage -induced apoptosis, the aim of this study was to assess the effect of cAMP-elevating agents on these proteins in doxorubicin-treated pre-B acute lymphoblastic leukemia (pre-B ALL) NALM-6 cells.The pre-B ALL cell line NALM-6 was cultured and treated with doxorubicin in combination with or without cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX). Cell viability was measured by trypan blue staining and MTT assay. For evaluation of apoptosis, annexin-V staining by flow cytometry and caspase-3 activity assay were used. Protein expression of p53, BAD and phoshorylated BAD was detected by western blotting analysis.cAMP-increasing agents diminished the doxorubicin-mediated cytotoxicity in NALM-6 cells as indicated by the viability assays. Annexin-V apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis. Moreover, doxorubicin-induced caspase-3 activity was attenuated in the presence of cAMP-increasing agents. Western blot results revealed the reduced expression of p53 protein in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone. Expression of total BAD protein was not affected by doxorubicin and cAMP-elevating agents. However, phosphorylation of BAD protein was induced in the presence of cAMP-elevating agents. Our study suggests that elevated cAMP levels inhibit doxorubicin-induced apoptosis in pre-B ALL cells through induction of BAD phosphorylation and abrogation of p53 accumulation.
Keywords: Doxorubicin, Apoptosis, cAMP, p53, BAD
Full-Text [PDF 301 kb]   (2073 Downloads)    
Type of Study: Original Article | Subject: Cancer
Received: 2014/12/6 | Accepted: 2015/03/16 | Published: 2015/05/22
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Fatemi A, Kazemi A, Kashiri M, Safa M. Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation. Int J Mol Cell Med. 2015; 4 (2) :94-102
URL: http://ijmcmed.org/article-1-264-en.html


Volume 4, Issue 2 (Int J Mol Cell Med 2015) Back to browse issues page
International Journal of Molecular and Cellular Medicine (IJMCM) International Journal of Molecular and Cellular Medicine (IJMCM)
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