Transferulic Acid Suppresses TNF α-induced β-Catenin Activation and Epithelial-Mesenchymal Transition in A549 Lung Cancer Cells

Abstract

Background and Objectives: Lung cancer is a prevalent malignancy characterized by a high propensity for metastasis and is a rising contributor to mortality. The prognosis and treatment strategies have become challenging due to its metastatic ability. Henceforth, our current work investigates the potential of Transferulic Acid (TRA) in suppressing Tumor Necrosis Factor alpha (TNFα) mediated activation of β-catenin and Epithelial-Mesenchymal Transition (EMT), especially in lung cancer cells (A549). TRA was selected because of its potential to simultaneously modulate inflammatory and oncogenic pathways involved in EMT progression, although evidence in TNFα-driven EMT suppression in lung cancer remains limited.Materials and Methods: MTT experiment was performed to demonstrate the cytotoxicity of TNFα-treated cells, TNFα + TRA-treated cells, and TRA alone-treated cells. To study the morphometric deformities of treated and control cells, AO and EtBr staining were carried out. Transwell migration and wound healing assays were conducted to determine the migration and invasion of A549 cells. Clonogenic and cell aggregation assays were carried out to disclose the proliferation capability. Indirect ELISA and qRT-PCR were carried out to investigate the expression of β-catenin in treated and control cells.Results: From the results of MTT, the IC50 of TRA was found at a concentration of 98.69 µg/mL. Late apoptotic cells with nuclear condensation were observed in the TNFα + TRA group. The findings of transwell migration and wound healing assays revealed that the TNFα + TRA group effectively inhibits cellular migration. Whereas, the results of clonogenic and cell aggregation assays indicate the inability of cells treated with TNFα + TRA to proliferate in an anchorage-independent environment and the inability to form colonies, respectively. Lastly, the gene expression studies indicated that the TNFα + TRA group downregulated beta catenin.Conclusion: Transferulic Acid (TRA) inhibits TNFα induced β-catenin activation, suppressing epithelial-mesenchymal transition, cell migration, and proliferation in A549 lung cancer cells. These outcomes indicate that TRA may serve as a promising therapeutic agent towards inflammation-driven lung cancer progression.

Keywords: Epithelial-Mesenchymal Transition; Lung Cancer; Metastasis; Transferulic Acid