Alpha-Lipoic Acid-Mediated Inhibition of LTB Synthesis Suppresses Epithelial-Mesenchymal Transition, Modulating Functional and Tumorigenic Capacities in Non-Small Cell Lung Cancer A549 Cells

Overview

Journal Curr Ther Res Clin Exp

Date 2025 Jan 16

PMID 39816494

Authors

Maria Jose Torres

Juan Carlos Rios

Alexandra Valle

Sebastian Indo

Kevin Brockway Gv

Fernanda Lopez-Moncada

Mario Faundez

Enrique A Castellon

Hector R Contreras

Affiliations

Soon will be listed here.

Abstract

Background: Leukotriene B (LTB) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB is mediated by leukotriene A hydrolase (LTAH), and it binds to the receptors BLT and BLT. Dysregulation in LTB production is linked to the development of various pathologies. Therefore, the identification or design of inhibitors of LTB synthesis or receptor antagonists represents an ongoing challenge. In this context, our laboratory previously demonstrated that alpha-lipoic acid (ALA) inhibits LTAH. The objective of this study was to evaluate the effect of ALA on the expression of canonical EMT markers and the functional and tumorigenic capacities induced by LTB in A549 cells.

Methods: The expression of cPLA, 5LOX, FLAP, LTAH, BLT1, and LTB production in human adenocarcinomic alveolar basal epithelial A549 cells was assessed using Western blot, RT-qPCR, and ELISA, respectively. Subsequently, the expression of canonical EMT markers was evaluated by Western blot. Functional assays were performed to assess cell viability, proliferation, invasion, migration, and clonogenicity using MTT, Western blot, Transwell assays, and colony formation assays, respectively. Results were expressed as median with interquartile range (n≥3) and analyzed using the Kruskal-Wallis or Tukey multiple comparisons tests.

Results: A549 cells express key proteins involved in LTB synthesis and receptor binding, including LTAH and BLT, and ALA inhibits the production of LTB. Additionally, LTAH and BLT1 were detected in lung adenocarcinoma tissue samples. LTB was found to induce EMT, whereas ALA treatment enhanced the expression of epithelial markers and reduced the expression of mesenchymal markers. Furthermore, ALA treatment resulted in a decrease in LTB levels and attenuated the functional and tumorigenic capacities of A549 cells, including their viability, migration, invasion, and clonogenic potential.

Conclusions: These findings suggest that ALA may offer therapeutic potential in the context of lung cancer, as it could be integrated into conventional pharmacological therapies to enhance treatment efficacy and mitigate the adverse effects associated with chemotherapy. Further studies are warranted to confirm the clinical applicability of ALA as an adjunctive treatment in lung cancer.

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