Quercetin Suppresses Migration and Promotes Mitochondrial Apoptosis Through KRAS-Associated Signaling in Caco-2 Colorectal Cancer Cells

Abstract

Colorectal cancer (CRC) remains a leading cause of cancer related mortality owing to uncontrolled proliferation, metastatic progression, and resistance to apoptosis. Quercetin, a naturally occurring dietary flavonoid, has attracted considerable interest as a potential anti-cancer agent. This study evaluated the anti-cancer effects of quercetin in Caco-2 colorectal adenocarcinoma cells by combining in vitro functional assays with molecular docking and in silico ADMET analyses. Cells were treated with 20 and 40 µM quercetin for 48 h, followed by assessment of cell viability, migration, apoptosis-related gene expression, and caspase-3/7 and caspase-9 activities. Molecular docking against KRAS^G12C (PDB ID: 6OIM) and ADMET prediction were performed to explore target binding and drug-like properties. Quercetin significantly reduced cell viability and migration, downregulated KRAS and BCL-2, and upregulated BAX, CASP3, CASP9, and TP53, accompanied by increased caspase-3/7 and caspase-9 activities, indicating activation of intrinsic mitochondrial apoptosis. Docking analysis predicted stable binding of quercetin to the KRAS^G12C binding pocket (−9.1 kcal/mol), while ADMET analysis suggested favorable drug-likeness and pharmacokinetic characteristics despite predicted cytochrome P450 interactions. Collectively, these findings indicate that quercetin suppresses CRC cell growth and migration while promoting apoptosis through modulation of KRAS-associated signaling, supporting its potential as a natural lead compound for colorectal cancer therapy and warranting further in vivo and pharmacokinetic validation.