Natural Monoterpene Stylosin Induced Anticancer Effects on Human Colon Carcinoma Cells.

Abstract

Colorectal carcinoma (CRC) ranks among the top five most common malignancies globally, characterized by a high incidence and poor prognosis. Hepatocyte growth factor receptor (HGFR), a tyrosine kinase oncoprotein, plays a critical role in tumor progression. This study aimed to investigate the effects of stylosin (STL), a natural monoterpene, on human CRC cells, with focus on its potential interactions with HGFR. For computational analysis, the expression of HGFR was assessed in CRC tissues, pharmacokinetics of STL were predicted, and the interaction between STL and HGFR was determined by molecular docking. For experimental studies, STL was isolated from Ferula ovina roots via thin layer chromatography, and its structure was confirmed by ¹H NMR spectroscopy. LoVo cells were treated with STL at concentrations of 25, 50, and 100 μM for 24, 48, 72, 96, and 120 h. Cell viability was assessed by alamarBlue, while apoptosis was evaluated by annexin V-FITC/PI staining followed by flow cytometry analysis. Results demonstrated significant overexpression of HGFR in CRC tissues relative to normal samples. The pharmacokinetic analysis of STL predicted high bioavailability, favorable distribution, and low toxicity risks. Molecular docking predicted a favorable binding affinity of STL to the active site of HGFR. Treatment with STL led to a dose-dependent decrease in cell viability, with the most pronounced cytotoxic effect observed at 100 μM. This was supported by notable morphological changes and increased apoptosis in treated cells. Collectively, the present findings show anticancer activity of STL in CRC cells, with computational predictions suggesting possible HGFR involvement and favorable pharmacokinetic properties. These results provide initial evidence supporting further investigation and position STL as a potent agent against CRC.