Iranian Biomedical Journal

en Targeting Metabolic Pathways in AML Cell Lines: Impact of Hypoxia-Inducible Factor-1α (HIF-1α) and Lactate Dehydrogenase-A (LDH-A) Inhibition Molecular Immunology & Vaccines Molecular Immunology & Vaccines مقاله کامل Full Length/Original Article <div style="text-align: justify;">Introduction: The Warburg effect is considered one of the most important metabolic alterations in tumor cells. While extensively studied in solid tumors, the role of this effect in acute myeloid leukemia (AML) is less defined. hypoxia inducible factor 1 alpha (HIF-1α) and lactate dehydrogenase A (LDH-A) are key regulators of glycolysis, promoting lactate production and the expression of lactate transporters. In this study, we examined the impact of HIF-1α and LDH-A inhibition on metabolic pathways, cell viability, and lactate transporter mRNA expression in AML cell lines. Methods: K-562 and HL-60 cells were treated with silibinin, an HIF-1α inhibitor, and sodium oxamate, a LDH-A inhibitor. Cell viability and apoptosis were evaluated using the MTT assay and flow cytometry, respectively. Acidification rate and LDH-A activity were assessed using lactate assay and LDH-A assay kits, respectively. Relative mRNA expression of MCT1 and MCT4 was determined using qRT-PCR. Results: Treatment with silibinin and sodium oxamate reduced proliferation and increased apoptosis in both K-562 and HL-60 cells. As expected, both agents decreased extracellular lactate release in K-562 cells, and sodium oxamate inhibited the LDH-A activity in both cell lines. Interestingly, the expression of MCT1, but not MCT4, was downregulated in K-562 cells after treatment. Conclusion: Our findings show that HIF-1α and LDH-A inhibitors not only serve as cytotoxic drugs but also regulate the expression of lactate transporter and interfere with the metabolism-related mechanisms in AML cells. </div> Acute myeloid leukemia, Hypoxia, Lactates, Warburg effect 427 436 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-6347-1&slc_lang=en&sid=1 Amir Kahrizi amirkahrizi2050@gmail.com 0009-0001-5740-3543 No Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Hossein Asgarian-Omran asgarianhossein@yahoo.com 0000-0003-3816-8792 No Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran Saeid Taghiloo Saeid.Taghiloo@gmail.com 0000-0002-8813-6046 No Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran Reza Valadan Valadan.Reza@gmail.com 0000-0002-9074-6994 No Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran Ahmad Najafi ahmad.najafi.2012@gmail.com 0000-0001-9821-336X No Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Armin Akbar arminakbar.br@gmail.com 0000-0002-8822-218X No Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Ehsan Zaboli paya_1358@yahoo.com 0000-0003-4009-717X No Department of Hematology and Oncology, Imam Khomeini hospital, Mazandaran University of Medical Sciences, Sari, Iran Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran Ramin Shekarriz drraminshekarriz@yahoo.com 0000-0002-0403-1109 No Department of Hematology and Oncology, Imam Khomeini hospital, Mazandaran University of Medical Sciences, Sari, Iran Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran Mohammad Eslami-Jouybari mo.eslami@mazums.ac.ir 0000-0001-5887-8869 No Department of Hematology and Oncology, Imam Khomeini hospital, Mazandaran University of Medical Sciences, Sari, Iran. Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Mohsen Tehrani drmtehrani@gmail.com 0000-0002-9292-4520 Yes Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran