Hesperidin and Diosmin Increased Cytotoxic Activity Cisplatin on Hepatocellular Carcinoma and Protect Kidney Cells Senescence.

Objective: Cisplatin (Cisp) is a chemotherapy drug for treating liver cancer. Hesperidin (HSD), a flavanone, is known for its anticancer, and anti-inflammatory properties. Diosmin (DSM), a flavone glycoside, is known for its anti-oxidant effect. This research investigated the synergism cytotoxic effect and senescence selectivity effect of HSD or DSM co-treatment with Cisp on HepG2 cells and Vero cells.

Methods: The cytotoxicity and cell viability of HSD or DSM combined with Cisp on HepG2 and Vero cells were assessed using the MTT assay with IC50 parameters, selectivity index (SI), and Combination Index (CI), while the antiproliferative profile was determined by colony-forming assay. Cellular senescence on HepG2 and Vero cell lines was determined using senescence-associated β-galactosidase (SA-β-gal) staining. Furthermore, the impact of apoptosis was evaluated using flowcitometry.

Result: In the MTT assay, HSD, DSM, and cisplatin exhibited cytotoxic effects on HepG2 cells, with IC50 values of 321 µM, 148 µM, and 5 µM, respectively. Co-treatment with HSD and DSM with cisplatin enhanced cell sensitivity, resulting in a combination index of < 1. HSD and DSM exhibited minimal cytotoxicity against Vero cells, with IC50 values exceeding 500 µM. Both HSD and DSM reduced cellular senescence in Vero cells caused by cisplatin exposure. These findings suggest that co-treatment with HSD and DSM alongside cisplatin can synergistically lessen the viability of HepG2 cells. The Annexin V-FITC/PI apoptosis assay also showed more cells undergoing apoptosis in the co-treatment group. Both co-treatment HSD and DSM with Cisp independently induced the senescence of HepG2 cells and reduced the cellular senescence of normal kidney cells.

Conclusion: Consequently, both HSD and DSM show potential for development as co-treatment agents in combination with Cisp for hepatocellular carcinoma, and they may also be useful for reducing senescence in normal kidney cells.