Iranian
Biomedical Journal
Volume 29, Issue 6 (11-2025)
IBJ 2025, 29(6): 427-436 |
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Kahrizi A, Asgarian-Omran H, Taghiloo S, Valadan R, Najafi A, Akbar A, et al . Targeting Metabolic Pathways in AML Cell Lines: Impact of Hypoxia-Inducible Factor-1α (HIF-1α) and Lactate Dehydrogenase-A (LDH-A) Inhibition. IBJ 2025; 29 (6) :427-436
URL: http://ibj.pasteur.ac.ir/article-1-5155-en.html
URL: http://ibj.pasteur.ac.ir/article-1-5155-en.html
Amir Kahrizi 
, Hossein Asgarian-Omran , Saeid Taghiloo , Reza Valadan , Ahmad Najafi , Armin Akbar , Ehsan Zaboli , Ramin Shekarriz , Mohammad Eslami-Jouybari , Mohsen Tehrani *
, Hossein Asgarian-Omran , Saeid Taghiloo , Reza Valadan , Ahmad Najafi , Armin Akbar , Ehsan Zaboli , Ramin Shekarriz , Mohammad Eslami-Jouybari , Mohsen Tehrani *
Abstract:
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 AML is less defined. HIF-1α and 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.
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.
Type of Study: Full Length/Original Article |
Subject:
Molecular Immunology & Vaccines
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