Flavonoids from Cirsium italicum (Savi) DC. reduce reactive oxygen species and modulate histone deacetylase activity in triple-negative breast cancer cells

Purpose: The present study aims to investigate the potential anti-cancer activities of flavonoid compounds from Cirsium italicum (Savi) DC. plants in breast cancer cells. Materials and Methods: MDA-MB-231 triple-negative breast cancer (TNBC) cells were used to demonstrate reactive oxygen species (ROS) production effects and histone deacetylase (HDAC) inhibitory activity of flavonoids [5,3',4'-trihydroxy-7-methoxy isoflavone (Santal) (1), 5,5'',7''-trihydroxy-3,7-dimethoxy-4',4'''-O-biflavone (2), 6-2ʹ-dihydroxy-5-methoxy isoflavonone-4ʹ-O-α-D-glucopyranoside (3), (8,3',4',5'-tetrahydroxy-7-O-α-glycosyl isoflavone)-6-8''-(4'''-hydroxy-7''-O-α-glycosyl isoflavone) biflavone (4)] isolated from C. italicum. Results: Significant differences in intracellular ROS levels were observed in MDA-MB-231 breast cancer cells treated with the compounds at concentrations of 0.06, 0.08, and 0.1 mg/ml. Compound 2 at 0.06 mg/ml, and compounds 2 and 4 at 0.08 and 0.1 mg/ml, induced a significant decrease in intracellular ROS levels compared to control cells. At a concentration of 0.06 mg/ml, compound 2 showed a mean value of 0.003±0.004. At 0.08 mg/ml, the mean values were 0.006±0.018 for compound 2 and 0.013±0.013 for compound 4. At 0.1 mg/ml, compound 2 and compound 4 exhibited mean values of 0.014±0.017 and 0.014±0.007, respectively. Even though all flavonoids inhibited HDAC activity, this inhibition was not statistically significant. Conclusion: Among the flavonoids isolated from C. italicum, compounds 2 and 4 showed potential anticancer effects in breast cancer cells, potentially through modulation of intracellular ROS levels.