E-Book 2nd Congress

  • Selumetinib, a promising small-molecule therapeutic: regulates apoptosis, autophagy, and reactive oxygen species pathways to the impairment of T-acute lymphoblastic leukemia cells
  • Faeze Bagherifar,1 Hussein Ayatollahi,2,* Pejman Hamdei_Asl,3 Sepide Shakeri,4
    1. Faculty of Medicine, Mashhad University of Medical Sciences
    2. Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences
    3. Department of Hematology and blood banking, School of Allied medical sciences, Iran university of medical sciences
    4. ARTA molecular hematology, genetic and transplantation central lab


  • Introduction: T-Acute Lymphoblastic Leukemia (T-ALL) is a hematological malignancy that has faced many challenges in treatment. The first line of therapy in T-ALL is glucocorticoids (GC). Unfortunately, after a while, some patients show resistance to GC therapy. This can be with early relapse and low survival rates. Furthermore, they have suffered many side effects. Recently, a novel treatment called targeted therapy has been developed. It includes a wide range of new treatments from immunotherapy to intracellular signaling pathway inhibitors, which act specifically and with high efficiency. In this study, we investigated the effects of Selumetinib as a MEK inhibitor on three major cellular pathways (i.e., apoptosis, autophagy, ROS) in T-ALL cells.
  • Methods: Jurkat cells were treated with different concentrations of Selumetinib. Then cell viability and IC50 value were measured by Alamar blue assay. Next, gene expression profiles (BCL-2, BAX, P53, BECN1, and NFE2L2) were assessed with Real-Time PCR and analyzes with REST 2009 (version 2.0.13). All data analysis was evaluated by Graphpad prism (version 9.4.0.673) software statically.
  • Results: The results revealed that Selumetinib increased BAX gene expression (p<0.05) and BAX/BCL-2 ratio in a time- and dose-dependent manner. Interestingly, BECN-1 expression was increased via BAX stimulation (p<0.001). In addition, an increase in the level of NFE2L2 (due to ROS accumulation) was observed in the treated group (p<0.001).
  • Conclusion: Our data showed expression levels of BAX, BECN1, and NFE2L2 genes were significantly increased in Jurkat cells. This suggests that Selumetinib causes apoptosis through the induction of autophagy and ROS pathways. This study highlights that Selumetinib has the potential to be a promising prospect in the treatment protocol of T-ALL patients as a combined therapy with GCs. However, more in vivo and in vitro investigations are still needed.
  • Keywords: Acute Lymphoblastic Leukemia, apoptosis, autophagy, reactive oxygen species, Selumetinib