Evaluation of supercritical fluid extracts of Cannabis sativa L. on colorectal cancer cells: Linking chemical composition with cytotoxic efficacy

Given the global burden of colorectal cancer, exploring natural therapeutics is essential. Cannabis sativa L., a rich source of bioactive secondary metabolites, includes cannabidiol and phenolic compounds. This study aimed to evaluate the impact of different supercritical fluid extraction conditions on the chemical profile and antineoplastic potency C. sativa extracts against colorectal cancer cells. Cannabidiol, total phenolic content, and total flavonoid content were quantified from varying extracts obtained via supercritical fluid extraction. Phenolics were identified using HPLC. The cytotoxic effects of the extracts were assessed on HCT-116 and HT-29 colorectal cancer cells. Results indicated that incorporating an ethanol modifier significantly increased bioactive recovery, with the extraction method (330 bar, 60 °C, +modifier) yielding the highest cannabidiol (0.039 ppm), total phenolic content (4.49 mg GAE/g DW), total flavonoid content (6.37 mg QE/g DW) and lowest DPPH IC50 value (1.87 mg/ml). HPLC identified quercetin and benzoic acid. All extracts exhibited dose-dependent cytotoxicity. HCT-116 cells showed higher sensitivity. Modulating extraction parameters influences the antiproliferative activity of C. sativa. Overall, these findings highlight the potential of co-solvent-assisted SFE for generating enriched botanical extracts with combined cytotoxic activity in preliminary cell-based models, supporting further research into green extraction technologies for oncological applications.