Berberine induces double-strand DNA breaks in Rev3 deficient cells

Berberine is a natural isoquinoline alkaloid, the majority of which is extracted from Huang Lian and other medicinal herbs. Numerous studies have revealed that berberine exhibits anticancer activity, however the mechanisms underlying this effect remain elusive. To examine these mechanisms, we analyzed the effects of berberine on a panel of DNA repair deficient chicken B lymphocyte (DT40) clones. Our results revealed that DT40 cells deficient in Rev3 (Rev3-/-), a translesion DNA synthesis (TLS) gene, were hypersensitive to berberine. Following berberine treatment, cell cycle analysis identified that G2/M arrest was increased in Rev3-/- cells. Furthermore, compared with wild-type cells (WT), berberine also induced a significant increase in double-strand breaks (DSBs) in Rev3-/- cells, as revealed by chromosomal aberration (CA) analysis. These results suggest that berberine is able to induce DNA damage, and that the Rev3 associated DNA repair pathway participates in the processes that aid its repair.