Evaluation of agmatine’s anti-cancer efficacy in Caco-2 colorectal adenocarcinoma cells

Abstract This study aimed to evaluate the potential effects of agmatine on cell viability, migration, invasion, apoptosis, and the expression of the ABCB1 , ABCC1 , and ABCG2 genes in the Caco-2 colon cancer cell line. Agmatine efficacy was assessed thruogh proliferation, migration, and invasion assays at various concentrations. The apoptotic index was determined using apoptosis-related markers ( Bax , Bcl-2 , Csp-3 ) via apoptosis assays, quantitative real-time PCR (qRT-PCR), and Western blot analysis. Expression levels of the ABCG2 , ABCB1 , and ABCC1 genes were measured by qRT-PCR in agmatine-treated Caco-2 cells. Oxidative stress markers, including glutathione peroxidase ( GPx ) and catalase ( CAT ), were evaluated by qRT-PCR. Cell viability analysis revealed that agmatine exerted its most pronounced effects at 72 h, with significant reductions at concentrations of 6, 7.3, and 9 mM in Caco-2 cells and 6, 6.25, and 9 mM in L929 cells ( p  < 0.05). At these concentrations, migration and invasion assays showed dose-dependent decreases in cell motility and invasiveness in Caco-2 cells. Apoptosis analysis demonstrated a significant increase in the apoptotic index with rising agmatine concentrations. Significant decreases in GPx and CAT were observed in all three agmatine-treated Caco-2 groups compared to untreated controls ( p  < 0.01). However, the expression levels of ABCG2 , ABCB1 , and ABCC1 showed no significant changes following agmatine treatment ( p  > 0.05). These findings indicate that agmatine exerts antiproliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in Caco-2 colon cancer cells, potentially through the modulation of apoptosis- and oxidative stress–related pathways. The lack of significant impacts on ABC transporter gene expression suggests that agmatine may be a promising candidate molecule for further translational studies in colorectal cancer.