Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells

Zhang, Zhuhong; Chen, Si; Mei, Hu; Xuan, Jiekun; Guo, Xiaoqing; Couch, Letha; Dobrovolsky, Vasily N.; Guo, Lei; Mei, Nan

doi:10.1038/srep14633

Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells

Journal Article · Wed Sep 30 00:00:00 EDT 2015 · Scientific Reports

DOI:https://doi.org/10.1038/srep14633· OSTI ID:1624799

Zhang, Zhuhong ^[1]; Chen, Si ^[2]; Mei, Hu ^[3]; Xuan, Jiekun ^[2]; Guo, Xiaoqing ^[4]; Couch, Letha ^[2]; Dobrovolsky, Vasily N. ^[4]; Guo, Lei ^[2]; Mei, Nan ^[4]

U.S. Food and Drug Administration (FDA), Jefferson, AR (United States). National Center for Toxicological Research. Division of Genetic and Molecular Toxicology; DOE/OSTI
U.S. Food and Drug Administration (FDA), Jefferson, AR (United States). National Center for Toxicological Research. Division of Biochemical Toxicology
Chongqing Univ. (China). College Bioengineering
U.S. Food and Drug Administration (FDA), Jefferson, AR (United States). National Center for Toxicological Research. Division of Genetic and Molecular Toxicology

Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available Ginkgo biloba extract product. Our findings suggest that Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be the result of Topo II inhibition.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 1624799

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 5; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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