Garambullo (Myrtillocactus geometrizans) reduces cell viability via apoptosis and inhibits colony formation in HT-29 and SW480 colon cancer cell lines.

Garambullo (Myrtillocactus geometrizans) is a Mexican wild fruit rich in phytochemicals. In this study, freeze-dried garambullo was subjected to in vitro gastrointestinal digestion and fermentation. The resulting fermented extract of garambullo (FEG) was evaluated for its effects on cell viability in HT-29 and SW480 CRC cell lines using MTT assays. After 24 h of treatment, FEG exhibited IC50 values of 2985 μg/mL and 3200 μg/mL in HT-29 and SW480 cells, respectively, indicating a significant reduction in cell viability compared to the control group. This reduction was further confirmed by flow cytometry, which revealed increased late apoptosis and necrosis in HT-29 cells, and a pronounced increase of necrosis in SW480 cells treated with FEG. Molecular docking simulations further supported these findings, demonstrating that butyric acid, a metabolite identified in FEG, demonstrates energetically favorable interactions with Caspase-3 (ΔG: -5.41 kcal/mol) and RIPK1 (ΔG: -5.18 kcal/mol), suggesting potential multi-pathway involvement in apoptotic and necrosis-associated cell death. Furthermore, the colony-forming ability of these CRC cell lines was assessed using 3D culture assays. After 14 days, FEG reduced colony formation in SW480 cells, with complete suppression observed at 149 μg/mL. Notably, HT-29 cells exhibited greater sensitivity, as no colonies were detected at any of the tested concentrations (≥37 μg/mL). These findings indicate that FEG exerts significant anti-proliferative, proapoptotic, and anti-clonogenic effects in CRC cell lines, supporting its potential as a candidate for further investigation in therapeutic or preventive strategies.