Hesperidin reduces genomic instability in glioblastoma cells and is associated with reduced HNRNPA2B1/m6A levels.

Genomic instability contributes to tumor progression and limits the effectiveness of anticancer therapy. In this study, we investigated whether the citrus flavonoid hesperidin influences cytogenetic damage and epitranscriptomic markers in tumor cells exposed to ionizing radiation or maintained under long-term culture conditions. In human glioblastoma cell lines U87MG and LN229, hesperidin reduced radiation-induced micronucleus formation and decreased the spontaneous micronucleus frequency during prolonged passaging with repeated supplementation. Immunocytochemical analysis demonstrated that long-term hesperidin treatment was accompanied by reduced HNRNPA2B1 protein expression and lower global m6A RNA levels. In a primary culture of collecting duct renal carcinoma cells, hesperidin altered cell morphology and growth dynamics during long-term cultivation. Together, these findings indicate that hesperidin reduces markers of genomic instability in tumor cell models and is accompanied by changes in HNRNPA2B1 expression and global m6A RNA methylation. The mechanistic relationship between these observations requires further investigation.