Cynara cardunculus subsp. cardunculus (Wild Artichoke) Extract: Antimicrobial Activity and Cytotoxicity, Apoptosis Induction, and Chemosensitization in Colon Cancer Cells

Colorectal cancer (CRC) is still a leading cause of cancer-related death worldwide, and often, conventional chemotherapeutics exhibit limited efficacy. The hydroalcoholic leaf extract of <i>Cynara cardunculus</i> subsp. <i>cardunculus</i> (wild artichoke) was investigated for its anticancer potential in CRC and effects on enteric pathogens. Nine phenolic compounds were identified by high-performance liquid chromatography with diode-array detection (HPLC-DAD), and spectrophotometric analyses were applied for total phenolic (TPC: 178.33 mg GAE/g) and total flavonoid (TFC: 52.21 mg CE/g) content quantification. The extract exhibited good antioxidant activity on DPPH (IC₅₀: 21.35 μg/mL), ^-•O₂ (IC₅₀: 1.56 μg/mL), and H₂O₂ (IC₅₀: 314.73 μg/mL) and was found to inhibit the growth of pathogenic enteric bacteria, with <i>Enterococcus faecalis</i> and <i>Staphylococcus aureus</i> being the most sensitive. In CaCo-2 CRC cells, the extract induced a concentration-dependent cytotoxicity (IC₅₀: 13.07 μg/mL at 24 h) through increased production of reactive oxygen species (ROS), upregulation of Nrf2, and induction of apoptosis, as evidenced by elevated p53, Bax, cytochrome c, and caspase-3 levels. No necrosis, measured by lactate dehydrogenase (LDH) release, or toxicity to HFF-1 normal fibroblasts was observed at concentrations up to 50 μg/mL. Additionally, CCE demonstrated synergistic effects with 5-FU (combination index < 0.8). This evidence suggests that CCE exhibits selective antitumor activity and chemosensitizing properties, supporting its possible development as an adjunctive agent in CRC therapy.