Inhibitory role of cAMP on doxorubicin-induced apoptosis in pre-B ALL cells through dephosphorylation of p53 serine residues |
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| Authors: | Majid Safa Ahmad Kazemi Hamid Zand Azita Azarkeivan Farhad Zaker Parisa Hayat |
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| Affiliation: | (1) Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, P.O. Box # 14155-6183, Tehran, Iran;(2) Department of Basic Medical Sciences, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University M. C., Tehran, Iran;(3) Iranian Blood Transfusion Organization Research Center, Tehran, Iran;(4) Cellular and Molecular Research Center, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran; |
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| Abstract: | Exposure of cells to chemotherapeutic drug doxorubicin, a DNA-damaging agent, induces an increase in the levels and activity of the wild-type p53 protein. Less well appreciated was the effect of cAMP levels on posttranslational modifications of p53 in response to doxorubicin. Here we show that elevation of cAMP in pre-B acute lymphoblastic leukemia NALM-6 cells significantly attenuated phosphorylation state of p53 at Ser6, Ser9, Ser15, Ser20, Ser37, Ser46 and Ser392 upon exposure to doxorubicin. Increased cAMP levels also shifted the ratio of the death promoter to death repressor genes via alteration of Bcl-2 and Bax proteins expression. In conclusion, our results suggest that activation of cAMP-signaling system may repress p53-dependent apoptosis in malignant cells exposed to doxorubicin. |
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