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Information Journal Paper

Title

SYNERGISTIC EFFECT OF SIMVASTATIN AND ROMIDEPSIN ON GAMMA-GLOBIN GENE INDUCTION

Pages

  576-583

Abstract

 Objective: Hemoglobinopathies such as BETA-THALASSEMIA and SICKLE CELL DISEASE (SCD) are inherited disorders that are caused by mutations in beta-globin chain. Gamma-globin gene reactivation can ameliorate clinical manifestations of betathalassemia and SCD. Drugs that induce fetal hemoglobin(HbF) can be promising tools for treatment of BETA-THALASSEMIA and SCD patients. Recently, it has been shown that SIMVASTATIN (SIM) and ROMIDEPSIN (ROM) induce HbF. SIM is aBCL11a inhibitor and ROM is aHDAC inhibitor and both of these drugs are Food and Drug Administration (FDA) -approved for hypercholesterolemia and cutaneous T-cell lymphoma respectively. Our aim was to evaluate the synergistic effects of these drugs in inducing HbF.Materials and Methods: In our experimental study, we isolated CD34+cells from five cord blood samples that were cultured in erythroid differentiation medium containing ROM and SIMVASTATIN. Then Gamma-globin, BCL11a and HDAC gene expression were evaluated on the 7th and 14th day of erythroid differentiation by real-time polymerase chain reaction (PCR) and immunocytochemistry.Results: Our results showed that combination of SIM and ROM significantly increased Gamma-globin gene expression and inhibitBCL11a and HDAC expression compared to results of using each of them alone. SIM and ROM lead to 3.09- fold increase in HbF production compared to the control group. Also, SIM inhibitedBCL11a expression (0.065-fold) and ROM inhibitedHDAC1 expression (0.47-fold) as two important inhibitors of HbF production after birth.Conclusion: We propose combination therapy of these drugs may be ameliorate clinical manifestation in BETA-THALASSEMIA and SCD with at least side effects and reduce the need for blood transfusion.

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    APA: Copy

    HABIBI, HUSSAIN, ATASHI, AMIR, ABROUN, SAEID, & NORUZINIA, MEHRDAD. (2019). SYNERGISTIC EFFECT OF SIMVASTATIN AND ROMIDEPSIN ON GAMMA-GLOBIN GENE INDUCTION. CELL JOURNAL (YAKHTEH), 20(4), 576-583. SID. https://sid.ir/paper/727938/en

    Vancouver: Copy

    HABIBI HUSSAIN, ATASHI AMIR, ABROUN SAEID, NORUZINIA MEHRDAD. SYNERGISTIC EFFECT OF SIMVASTATIN AND ROMIDEPSIN ON GAMMA-GLOBIN GENE INDUCTION. CELL JOURNAL (YAKHTEH)[Internet]. 2019;20(4):576-583. Available from: https://sid.ir/paper/727938/en

    IEEE: Copy

    HUSSAIN HABIBI, AMIR ATASHI, SAEID ABROUN, and MEHRDAD NORUZINIA, “SYNERGISTIC EFFECT OF SIMVASTATIN AND ROMIDEPSIN ON GAMMA-GLOBIN GENE INDUCTION,” CELL JOURNAL (YAKHTEH), vol. 20, no. 4, pp. 576–583, 2019, [Online]. Available: https://sid.ir/paper/727938/en

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