Antitumor effects of diosmetin in Ehrlich ascites carcinoma mouse model: insights into ROS-mediated mechanisms.

Abstract

Cancer remains one of the leading global health challenges, highlighting the continuous need for innovative therapeutic approaches. In this context, medicinal plants have been recognized as potential candidates for developing bioactive compounds, including flavonoids, which have demonstrated good anticancer properties. Diosmetin, a flavonoid aglycone predominantly found in citrus fruits, has shown potent anticancer properties due to its ability to induce cell cycle arrest, induce apoptosis, and inhibit tumor progression. This study evaluates the anticancer potential of diosmetin across various cancer cell lines such as prostate, skin, liver, lung, and in a murine Ehrlich ascites carcinoma (EAC) model. The cytotoxic effects of diosmetin were assessed by using three independent assays like SRB, MTT, and NRU. Diosmetin exhibited potent antiproliferative effects, with the lung and hepatic cancer cell lines showing the highest sensitivity. Furthermore, in the EAC mouse model, diosmetin significantly reduced tumor growth and promoted cell death. Mechanistic investigations revealed that diosmetin increases reactive oxygen species (ROS) generation in tumor cells. This is further confirmed by co-treatment with N-acetyl cysteine (NAC), a ROS inhibitor. Additionally, diosmetin demonstrated favorable pharmacokinetic and drug-likeness properties, including high gastrointestinal absorption and non-toxicity towards human erythrocytes. These findings suggest that diosmetin holds considerable promise as a potential anticancer agent, warranting further investigation for its therapeutic development.