| چکیده انگلیسی مقاله |
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. |
| نویسندگان مقاله |
| Amir Kahrizi
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| Hossein Asgarian-Omran
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
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
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
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| Armin Akbar
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| Ehsan Zaboli
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
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
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
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
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