Decoding the Anti-Tumour Mechanism of ɑ-Solanine: SRC Inhibition and Ferroptosis Induction in Colon Cancer

Abstract

α-Solanine, a steroidal alkaloid glycoside, exhibits significant anti-tumour properties with potential therapeutic applications in colon cancer. Its relevance was explored through network pharmacology, bioinformatics analysis and experimental validation. α-Solanine treatment significantly inhibited HT29 colon cancer cell proliferation and migration dose-dependently, reducing Ki67 and PCNA expression markers. Target prediction using PharmMapper and GeneCards databases revealed 90 potential targets, with network analysis identifying SRC as the key molecular target. Molecular docking confirmed stable α-solanine-SRC binding (−9.3 kcal/mol). TCGA analysis demonstrated SRC upregulation in colon cancer across tumour stages T1–T4, with high expression correlating negatively with immune infiltration and poor prognosis. Pathway analysis revealed SRC's involvement in PI3K/AKT/mTOR signalling, regulating ferroptosis-related genes. Experimental validation showed α-solanine increased ROS, MDA and iron levels while decreasing GSH, promoting ferroptosis. Gene silencing confirmed SRC's critical role in cancer progression, with α-solanine's effects suppressed upon SRC upregulation. These findings suggest that SRC is a potential target of α-solanine, and that its anticancer effects may involve inhibition of SRC and suppression of the PI3K/AKT/mTOR pathway. The ferroptosis-mediated mechanisms highlight α-solanine's therapeutic potential and suggest promising avenues for colon cancer treatment development.