Exploring the Effect of Lutein on TGF-β/ SMAD2 Signalling Molecule Gene Expression in Lung Cancer Cells: An In-vitro Study

Abstract

Introduction: Lung cancer is one of the most prevalent and deadly forms of cancer worldwide, accounting for a significant number of cancer-related deaths. Despite advances in diagnosis and treatment, the prognosis for lung cancer remains poor, emphasising the need for alternative and complementary therapeutic approaches. Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine that plays a crucial role in cell growth, differentiation, apoptosis and immune regulation. Suppressor of Mothers against Decapentaplegic (SMAD), a well known transcription factor, plays an essential role in carcinogenesis. Lutein, a naturally occurring carotenoid. Recent studies have suggested that lutein possess anticancer properties and could potentially be used as a therapeutic agent against various types of cancer. Aim: To assess the effect of lutein on TGF-β/SMAD2 gene expression in lung cancer cells. Materials and Methods: The present in-vitro study was carried in the Cancer and Stem Cell Laboratory Facility, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India, from April 2023 to May 2023. The lung cancer cell line (A-549) was obtained from the National Centre for Cell Science (NCCS), Pune, India. Cell viability of lutein-treated lung cancer cells was assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell morphology was studied using a phase contrast microscope. The gene expression of TGF-β/SMAD2 was analysed using real-time Polymerase Chain Reaction (PCR), and the results were presented graphically as fold change. All data obtained were analysed by one-way Analysis of Variance (ANOVA) followed by Student’s t-test using PRISM software version 4. Results: The findings suggest that lutein had good cytotoxic effects on lung cancer cells. The Half-maximal inhibitory concentration (IC50) value was found to be 5.14 μM/mL. Lutein inhibited the TGF-β and SMAD2 gene expression signalling pathway and induced apoptosis in A549. Conclusion: Lutein significantly inhibited the TGF-β and SMAD2 gene expression signalling pathways, making it a potent anticancer drug. The downregulation of key genes involved in the TGF-β/SMAD2 pathway suggests a nuanced and intricate relationship between lutein and the regulatory mechanisms governing cellular signalling in lung cancer. These findings support the notion that lutein may exert a regulatory influence on the intricate balance of signalling cascades, offering a potential avenue for therapeutic intervention in lung cancer.

Keywords

• signalling cascade
• suppressor of mothers against deccapentaplegic
• transforming growth factor-beta