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

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FATEMI AHMAD; KAZEMI AHMAD; KASHIRI MEYSAM; SAFA MAJID

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Journal: International Journal of Molecular and Cellular Medicine Year:2015 | Volume:4 | Issue:2 Page(s): 94-102

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Title

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

Author(s)

FATEMI AHMAD | KAZEMI AHMAD | KASHIRI MEYSAM | SAFA MAJID | Issue Writer Certificate

Keywords

DOXORUBICIN

APOPTOSIS

CAMP

P53

BAD

Abstract

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 CAMPelevating 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.

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APA: Copy

FATEMI, AHMAD, KAZEMI, AHMAD, KASHIRI, MEYSAM, & SAFA, MAJID. (2015). 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. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE, 4(2), 94-102. SID. https://sid.ir/paper/332157/en

Vancouver: Copy

FATEMI AHMAD, KAZEMI AHMAD, KASHIRI MEYSAM, SAFA MAJID. 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. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE[Internet]. 2015;4(2):94-102. Available from: https://sid.ir/paper/332157/en

IEEE: Copy

AHMAD FATEMI, AHMAD KAZEMI, MEYSAM KASHIRI, and MAJID SAFA, “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,” INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE, vol. 4, no. 2, pp. 94–102, 2015, [Online]. Available: https://sid.ir/paper/332157/en

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