β-sitosterol suppresses fibroblast growth factor and epidermal growth factor receptors to induce apoptosis and inhibit migration in lung cancer: an in vitro study.

Abstract

β-Sitosterol (BS), is a significant bioactive component of phytosterols found in plants, foods, and dietary supplements. Its nutritional benefits include lowering of cholesterol levels, boost immune system as well as reduce inflammation. Previous studies have demonstrated its significant anticancer effects across various human cancers. However, the specific mechanisms of action of BS in lung cancer remain unclear. This study aimed to investigate the mechanisms through which BS exerts its anticancer properties in human lung cancer cells, focusing on its anti-proliferative, apoptotic, cytotoxic, and anti-migratory effects. We conducted an in vitro study to assess the effects of BS on lung cancer cell lines A549 and H1975. We used a range of assays, including MTT, western blot, wound healing, transwell migration, immunofluorescence, TUNEL, and cell survival assays, to evaluate the impact of BS on cell proliferation, apoptosis, cytotoxicity, and migration. Our findings indicate that BS inhibits the proliferation of lung cancer cells in a time- and dose-dependent manner. It significantly promotes apoptosis and impairs both cancer cell migration and survival. Additionally, BS suppresses the expression of both fibroblast growth factor receptor-1 (FGFR1) and epidermal growth factor (EGFR), leading to the downregulation of the PI3K/AKT/mTOR/CD1 signaling pathway. BS demonstrates significant anticancer potential in lung cancer cells by inhibiting proliferation, inducing apoptosis, and reducing cell migration. These effects are likely mediated by the concurrent downregulation of FGFR1 and EGFR, leading to the inhibition of the PI3K/AKT/mTOR/CD1 signaling pathway, thereby warranting further investigation of BS as a potential therapeutic agent for lung cancer.