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Article

Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors

  • Authors:
    • Siavash Mansouri
    • Ali Shahriari
    • Hadi Kalantar
    • Taraneh Moini Zanjani
    • Mojtaba Haghi Karamallah
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Khuzestan 61357‑83151, Iran, Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Khuzestan 61357-33184, Iran, Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19857‑17443, Iran, Department of Biochemistry and Molecular Biology, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd 89151‑73143, Iran
  • Pages: 463-467
    |
    Published online on: March 14, 2017
       https://doi.org/10.3892/br.2017.873
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Abstract

High aerobic glycolysis, as one of the hallmarks of cancer cells, requires nicotinamide adenine dinucleotide (NAD+) as a vital co‑factor, to guarantee the flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer metabolism, is a source of NAD+ additional to lactate dehydrogenase (LDH). The current study aimed to elucidate the kinetic parameters of MDH in human breast cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis‑Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the crude extracts of human breast tumors and healthy tissue samples, which were obtained directly from the operating theatre. To assess the potential role of MDH in supporting glycolysis, the MDH activity was measured when the LDH activity was inhibited by different concentrations of oxamate, an inhibitor of LDH in breast cancer cell lines. The Km of cancerous MDH (C‑MDH) was the same as the healthy MDH, although the Vmax of C‑MDH was higher relative to the healthy MDH. Notably, the MDH activity was increased in the MDA‑MB‑231 cell line, which was treated with the LDH inhibitor (oxamate), but not in the MCF‑7 cell line (P<0.05). The higher tendency of C‑MDH for NAD+ and malate generation in cancer cells is an effective approach for supporting glycolysis. Increasing MDH activity in the absence of LDH demonstrates the supportive role of MDH in glycolysis. Therefore, decreasing MDH activity and expression in a forward reaction may present as a valid molecular target to abolish its potential effect on tumor metabolism.
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Copy and paste a formatted citation
Spandidos Publications style
Mansouri S, Shahriari A, Kalantar H, Moini Zanjani T and Haghi Karamallah M: Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors. Biomed Rep 6: 463-467, 2017.
APA
Mansouri, S., Shahriari, A., Kalantar, H., Moini Zanjani, T., & Haghi Karamallah, M. (2017). Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors. Biomedical Reports, 6, 463-467. https://doi.org/10.3892/br.2017.873
MLA
Mansouri, S., Shahriari, A., Kalantar, H., Moini Zanjani, T., Haghi Karamallah, M."Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors". Biomedical Reports 6.4 (2017): 463-467.
Chicago
Mansouri, S., Shahriari, A., Kalantar, H., Moini Zanjani, T., Haghi Karamallah, M."Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors". Biomedical Reports 6, no. 4 (2017): 463-467. https://doi.org/10.3892/br.2017.873
Copy and paste a formatted citation
x
Spandidos Publications style
Mansouri S, Shahriari A, Kalantar H, Moini Zanjani T and Haghi Karamallah M: Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors. Biomed Rep 6: 463-467, 2017.
APA
Mansouri, S., Shahriari, A., Kalantar, H., Moini Zanjani, T., & Haghi Karamallah, M. (2017). Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors. Biomedical Reports, 6, 463-467. https://doi.org/10.3892/br.2017.873
MLA
Mansouri, S., Shahriari, A., Kalantar, H., Moini Zanjani, T., Haghi Karamallah, M."Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors". Biomedical Reports 6.4 (2017): 463-467.
Chicago
Mansouri, S., Shahriari, A., Kalantar, H., Moini Zanjani, T., Haghi Karamallah, M."Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors". Biomedical Reports 6, no. 4 (2017): 463-467. https://doi.org/10.3892/br.2017.873
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