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

## TL;DR

Wild artichoke extract shows promise in killing colon cancer cells without harming healthy cells and enhances chemotherapy effectiveness.

## Contribution

The study demonstrates the selective antitumor and chemosensitizing properties of wild artichoke extract in colon cancer.

## Key findings

- Wild artichoke extract induces apoptosis in colon cancer cells without affecting normal cells at lower concentrations.
- The extract synergizes with 5-fluorouracil, reducing the required dose by tenfold.
- The extract inhibits growth of enteric pathogens like Enterococcus faecalis and Staphylococcus aureus.

## Abstract

Colorectal cancer is a major health problem worldwide and one of the top causes of cancer deaths. Treatments like chemotherapy are the gold standard, but they have limitations, especially in advanced cases, where cancer cells can become resistant to the treatment. Moreover, these approaches can harm healthy cells, leading to unpleasant side effects. To find a possible solution, we tested an extract from wild artichoke leaves, a plant from the Mediterranean region that contains health-promoting substances called polyphenols, to explore whether it could kill isolated cancer cells without affecting normal cells. Interestingly, our results showed that the extract can disrupt the inner balance of cancer cells, leading to apoptosis. Notably, normal cells were unaffected by the treatment, except at a concentration of 100 μg/mL. Additionally, we also observed that when combined with the commonly used chemotherapeutic 5-fluorouracil, the extract enhances the drug efficacy reducing the concentration necessary to exert its activity by about ten times (IC50 5-FU alone 5.46 μg/mL; IC50 0.5 μg/mL in combination with CCE 5.88 μg/mL). Moreover, we also observed that the extract inhibits the growth of enteric pathogens. These results suggest that wild artichoke extract could help make cancer treatments safer and more effective by improving chemotherapy and reducing side effects, offering a new natural option to fight this serious disease.

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 Cynara cardunculus subsp. cardunculus (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 Enterococcus faecalis and Staphylococcus aureus 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.