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International Journal of Molecular and Cellular Medicine، جلد ۴، شماره ۲، صفحات ۹۴-۱۰۲
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عنوان انگلیسی 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
چکیده انگلیسی مقاله 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.
کلیدواژه‌های انگلیسی مقاله Doxorubicin, Apoptosis, cAMP, p53, BAD
نویسندگان مقاله احمد فاطمی | ahmad fatemi
department of hematology, school of allied medicine, iran university of medical sciences, tehran, iran.

سازمان اصلی تایید شده: دانشگاه علوم پزشکی ایران (Iran university of medical sciences)

احمد کاظمی | ahmad kazemi
department of hematology, school of allied medicine, iran university of medical sciences, tehran, iran.

سازمان اصلی تایید شده: دانشگاه علوم پزشکی ایران (Iran university of medical sciences)

میثم کشیری | meysam kashiri
department of hematology, school of allied medicine, iran university of medical sciences, tehran, iran.

سازمان اصلی تایید شده: دانشگاه علوم پزشکی ایران (Iran university of medical sciences)

مجید صفا | majid safa
department of hematology, school of allied medicine, iran university of medical sciences, tehran, iran.

سازمان اصلی تایید شده: دانشگاه علوم پزشکی ایران (Iran university of medical sciences)
سازمان های دیگر: Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.

نشانی اینترنتی http://www.ijmcmed.org/browse.php?a_code=A-10-353-1&slc_lang=en&sid=en
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