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The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells in vitro highlights a new role for lactate

  • Authors:
    • Maitham A. Khajah
    • Sarah Khushaish
    • Yunus A. Luqmani
  • View Affiliations / Copyright

    Affiliations: College of Pharmacy, Kuwait University, Safat 13110, Kuwait
    Copyright: © Khajah et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 12
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    Published online on: November 22, 2023
       https://doi.org/10.3892/mmr.2023.13135
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Abstract

Lactate dehydrogenase (LDH) is being increasingly recognized as a major factor in the progression of breast cancer. It was previously shown that short interfering RNA‑mediated knockdown of either LDH‑A or ‑B isoform resulted in inhibition of cell motility due to reduced lactate levels in the extracellular environment. The aim of the present study was to determine the use of pharmacological LDH inhibitors to reduce aggressive behavior of breast cancer cells. The effect of LDH inhibitors was investigated in both estrogen receptor (ER)+ and ER‑ breast cancer cell lines and in normal breast epithelial cells. Cell proliferation, motility and invasion were measured using MTT, wound healing and cultrex assays, respectively. Changes in several key mediators of mitogenic signaling important in breast cancer cells were determined using western blotting. Treatment with various inhibitors reported to block LDH activity resulted in significant reduction in extracellular lactate level, cell proliferation, motility and invasion. This was associated with changes in the levels of vimentin, E‑cadherin, p38 MAPK, ERK1/2 and AKT. A couple of these inhibitors such as quercetin and lonidamine showed preferential inhibition of cancer cell proliferation compared with normal epithelial cell inhibition. These data extend initial findings, further underlining the importance of lactate as a major factor in breast cancer progression and indicate the practical use of various commercially available LDH inhibitors as promising therapeutic agents to oppose the processes leading to cancer progression.
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Spandidos Publications style
Khajah MA, Khushaish S and Luqmani YA: The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate. Mol Med Rep 29: 12, 2024.
APA
Khajah, M.A., Khushaish, S., & Luqmani, Y.A. (2024). The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate. Molecular Medicine Reports, 29, 12. https://doi.org/10.3892/mmr.2023.13135
MLA
Khajah, M. A., Khushaish, S., Luqmani, Y. A."The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate". Molecular Medicine Reports 29.1 (2024): 12.
Chicago
Khajah, M. A., Khushaish, S., Luqmani, Y. A."The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate". Molecular Medicine Reports 29, no. 1 (2024): 12. https://doi.org/10.3892/mmr.2023.13135
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Spandidos Publications style
Khajah MA, Khushaish S and Luqmani YA: The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate. Mol Med Rep 29: 12, 2024.
APA
Khajah, M.A., Khushaish, S., & Luqmani, Y.A. (2024). The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate. Molecular Medicine Reports, 29, 12. https://doi.org/10.3892/mmr.2023.13135
MLA
Khajah, M. A., Khushaish, S., Luqmani, Y. A."The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate". Molecular Medicine Reports 29.1 (2024): 12.
Chicago
Khajah, M. A., Khushaish, S., Luqmani, Y. A."The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells <em>in vitro</em> highlights a new role for lactate". Molecular Medicine Reports 29, no. 1 (2024): 12. https://doi.org/10.3892/mmr.2023.13135
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