Diosmin induces genotoxicity and apoptosis in DU145 prostate cancer cell line

Area of Science:

• * Nutritional biochemistry
• * Molecular oncology

Background:

• * Plant-derived polyphenols, especially flavonoids, show promise as anticancer agents due to their pro-apoptotic and chemopreventive properties.
• * The potential for flavonoid-induced genotoxicity to trigger cancer cell death warrants investigation.

Purpose of the Study:

• * To investigate the cyto- and genotoxicity of naringin, diosmin, and hesperidin in DU145 prostate cancer cells.
• * To determine if flavonoid-induced genotoxicity contributes to cancer cell death.

Main Methods:

• * Cytotoxicity and genotoxicity assays on DU145 cells treated with flavonoid glycosides.
• * Measurement of reactive oxygen species (ROS) and superoxide production.
• * Assessment of DNA double-strand breaks (DSBs) and micronuclei formation.
• * Analysis of 53BP1 recruitment and DNA/chromosomal damage.
• * Evaluation of DNA hypomethylation and epigenetic modulation.

Main Results:

• * Flavonoid glycosides reduced cancer cell number and proliferation.
• * Treatment increased intracellular ROS and superoxide levels.
• * Flavonoids induced DSBs and micronuclei production, with diosmin being the most potent genotoxic agent.
• * Diosmin exhibited pro-apoptotic activity, linked to its genotoxicity.
• * Naringin and hesperidin showed less DNA damage compared to diosmin.
• * Flavonoids acted as DNA hypomethylating agents, altering gene expression.

Conclusions:

• * Diosmin, a dietary flavonoid glycoside, demonstrates anticancer activity against DU145 cells by inducing genotoxicity and apoptosis.
• * Flavonoid-induced genotoxicity is a mechanism contributing to cancer cell death.
• * Further in vitro and in vivo studies on diosmin's biological activity against cancer cells are recommended.