title: Berberine induces double-strand DNA breaks in Rev3 deficient cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.affiliation: Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Regenerative Medicine Research Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qing
mesh_terms: D001599:Berberine / Q000633:toxicity*; D002460:Cell Line; D019457:Chromosome Breakage / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency*; D004351:Drug Resistance / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D001599:Berberine; D004259:DNA-Directed DNA Polymerase; C118285:REV3L protein, human