Alpha-Lipoic Acid-Mediated Inhibition of LTB4 Synthesis Suppresses Epithelial-Mesenchymal Transition, Modulating Functional and Tumorigenic Capacities in Non-Small Cell Lung Cancer A549 Cells

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dc.article.number100765
dc.catalogadorvzp
dc.contributor.authorTorres Torres, María José
dc.contributor.authorRios Bustamante, Juan Carlos
dc.contributor.authorValle Miranda, Alexandra Belén
dc.contributor.authorIndo, Sebastián
dc.contributor.authorBrockway Valenzuela, Kevin Sebastian
dc.contributor.authorLopez-Moncada, Fernanda
dc.contributor.authorFaundez Cáceres, Mario Antonio
dc.contributor.authorCastellón, Enrique A.
dc.contributor.authorContreras, Héctor R.
dc.date.accessioned2025-05-12T15:50:28Z
dc.date.available2025-05-12T15:50:28Z
dc.date.issued2025
dc.description.abstractBackground: Leukotriene B4 (LTB4) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB4 is mediated by leukotriene A4 hydrolase (LTA4H), and it binds to the receptors BLT1 and BLT2. Dysregulation in LTB4 production is linked to the development of various pathologies. Therefore, the identification or design of inhibitors of LTB4 synthesis or receptor antagonists represents an ongoing challenge. In this context, our laboratory previously demonstrated that alpha-lipoic acid (ALA) inhibits LTA4H. 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 LTB4 in A549 cells. Methods: The expression of cPLA2, 5LOX, FLAP, LTA4H, BLT1, and LTB4 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 LTB4 synthesis and receptor binding, including LTA4H and BLT1, and ALA inhibits the production of LTB4. Additionally, LTA4H and BLT1 were detected in lung adenocarcinoma tissue samples. LTB4 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 LTB4 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.
dc.fechaingreso.objetodigital2025-05-12
dc.format.extent14 páginas
dc.fuente.origenSCOPUS
dc.identifier.doi10.1016/j.curtheres.2024.100765
dc.identifier.issn18790313 0011393X
dc.identifier.scopusidSCOPUS_ID:85212575250
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/104134
dc.information.autorucEscuela de Química; Torres Torres, María José; S/I; 186677
dc.information.autorucEscuela de Medicina; Ríos Bustamante, Juan Carlos; 0000-0003-0701-9604; 104168
dc.information.autorucEscuela de Química; Valle Miranda, Alexandra Belén; S/I; 1066488
dc.information.autorucEscuela de Química; Brockway Valenzuela, Kevin Sebastián; S/I; 1066457
dc.information.autorucEscuela de Química; Faundez Cáceres, Mario Antonio; 0000-0002-5507-3579; 174901
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherElsevier Inc.
dc.revistaCurrent Therapeutic Research - Clinical and Experimental
dc.rightsacceso abierto
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International (C BY-NC-ND 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAlpha lipoic acid (ALA)
dc.subjectEpithelial Mesenchymal Transition (EMT) and Functional and tumor capacities
dc.subjectLeukotriene A4Hydrolase (LTA4H)
dc.subjectLeukotriene B4(LTB4)
dc.subjectSmall cell lung carcinoma and non-small cell lung cancer (NSCLC)
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAlpha-Lipoic Acid-Mediated Inhibition of LTB4 Synthesis Suppresses Epithelial-Mesenchymal Transition, Modulating Functional and Tumorigenic Capacities in Non-Small Cell Lung Cancer A549 Cells
dc.typeartículo
dc.volumen102
sipa.codpersvinculados186677
sipa.codpersvinculados104168
sipa.codpersvinculados1066488
sipa.codpersvinculados1066457
sipa.codpersvinculados174901
sipa.trazabilidadSCOPUS;2025-01-05
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