Combined anticancer effects of <i>Chamaecytisus hirsutus</i> extract and photodynamic therapy in Gastric cancer cells

The particular plant found in Türkiye, <i>Chamaecytisus hirsutus</i> ;(Fabaceae), has no studies examining its biological effects. Thus, the present study aimed to investigate the phytochemical composition, chemical profile, antioxidant activity, xanthine oxidase inhibition, anticancer effects, and photodynamic therapy potential of <i>C. hirsutus</i> methanol extract. Gas chromatography-mass spectrometry (GC-MS) analysis identified important compounds such as laminitol (28.74%), quinolinic acid (20.23%), and 2-(1,3-Dioxan-2-yl) ethanol (17.27%). The IC₅₀ value of the extract in the DPPH assay was 378.77 ± 4.70 mg/mL, demonstrating significant antioxidant activity. The xanthine oxidase inhibition was found to be 45.75 ± 2.59%, indicating significant free radical scavenging activity. The total phenolic, flavonoid, flavanols, and tannin contents were determined to be 35.14 ± 2.60 mg GAE/g extract, 12.90 ± 0.27 mg QE/g extract, 20.67 ± 0.81 mg QE/g extract, and 2.49 ± 0.12 mg GAE/g extract, respectively. The extract reduced the viability of MKN28 cancer cells by approximately 85% at a concentration of 0.4 mg/mL, demonstrating significant anticancer activity. Combination therapy with photodynamic therapy further enhanced the cytotoxic effect. Additionally, the binding affinities of these compounds with the 1GUX target protein were evaluated using molecular docking, and 4-Methyl-2-pentadecyl-1,3-dioxolane and Laminitol were determined as the strongest inhibitors with binding energies of -6.9 kcal/mol and -6.1 kcal/mol, respectively. Molecular dynamics simulations confirmed the stability of these interactions, with 4-Methyl-2-pentadecyl-1,3-dioxolane emerging as the compound with the strongest binding affinity. These findings suggest that <i>C. hirsutus</i> extract has the potential to be a powerful anticancer agent when used in photodynamic therapy.