Evaluation of Cytotoxicity and Antiproliferative Activity of Exopolysaccharides from Coelastrella sp. BGV in Human Cancer Cell Models: Mechanistic Insights from Integrated In Vitro and In Silico Studies

Exopolysaccharides (EPS) from microalgae have emerged as promising natural anticancer agents owing to their selective cytotoxicity toward tumor cells and low toxicity to healthy tissues. However, the molecular mechanisms and targets underlying their anticancer activity remain poorly understood. In the present study, EPS isolated from Coelastrella sp. BGV was evaluated for cytotoxicity and antiproliferative activity against a panel of human cancer cell lines (HepG2, HCT116, A549, and MDA-MB-231). The effects of EPS on mitochondrial function, cell cycle progression, apoptosis, and autophagy were investigated using flow cytometry and fluorescence microscopy. To gain mechanistic insight, molecular docking of a representative EPS disaccharide, α-L-Fucp-(1→6)-β-D-Galp, was performed against DC-SIGN and galectin-3 using the CB-Dock2 platform with the AutoDock Vina engine. The EPS exhibited minimal cytotoxicity toward non-tumor cells, and induced significant concentration-dependent antiproliferative activity in all tested cancer cell lines. MDA-MB-231 breast cancer cells were the most sensitive, with an IC50 value of 57.5 ± 10 µg/mL and a selectivity index of 5.2 relative to non-tumor cells. Mechanistically, EPS treatment induced mitochondrial membrane depolarization, S-phase cell cycle arrest, autophagy, and apoptosis, as demonstrated by nuclear fragmentation, chromatin condensation, and increased Annexin V positivity. Molecular docking identified DC-SIGN and galectin-3 as plausible molecular targets, suggesting potential anticancer activity of Coelastrella sp. BGV EPS that may involve both direct pro-apoptotic effects and modulation of carbohydrate-mediated signaling pathways. Collectively, these findings provide new mechanistic insight into the anticancer activity of Coelastrella sp. BGV EPS and support its further investigation as a promising natural candidate for adjunctive cancer therapy.