Synergistic Antineoplastic and Immunomodulatory Effects of Hesperidin in Ehrlich Ascites Carcinoma Tumor Model Treated with Cisplatin

Abstract

Despite substantial advancements in cancer research in recent years, the treatment of cancer remains fraught with difficulties. Cisplatin is a strong chemotherapeutic drug used to treat a variety of cancers, but its efficacy is limited by drug resistance and toxic effects on non-tumor tissues. The flavonoid hesperidin was reviewed to have anticancer properties. In the present study, a tumor model was established, cisplatin plus hesperidin synergism was conducted, antineoplastic and immunomodulatory effects were evaluated; oxidative stress markers and liver and kidney function tests were measured after mono and combined treatments. The mechanisms of hesperidin synergistic role with cisplatin chemotherapy were explored using ninety mice divided equally into nine groups. The findings indicated that hesperidin treatment alone, or in combination with cisplatin, inhibited tumor growth by causing cell cycle arrest, stimulating apoptosis, and reducing tumor cell proliferation. Furthermore, it stimulated anti-tumor immunity by increasing the proportion of T cytotoxic (CD3 + CD8 + ) and T helper (CD3 + CD4 + ) cells in the spleen with modulating effect on CD4 + CD25 + regulatory cells accompanied by improving spleen cells proliferation. Moreover, a significant increase in IFN-γ and granzyme B levels of tumorized mice co-treated with 100 or 200 mg/kg hesperidin plus cisplatin was demonstrated. Interestingly, the use of hesperidin in combined treatment succeeded to counteract toxic effects induced by cisplatin on normal healthy tissues. In conclusion, the combined use of hesperidin and cisplatin has a synergistic effect that enhances the efficacy of cancer treatment by inducing apoptosis and regulating the immune response against cancer cells. Additionally, this combination therapy reduces the harmful effects of cisplatin on healthy tissues.