title: Effect of fumonisin B₁ on the cell cycle of normal human liver cells.
abstract: Fumonisin B1 (FB1) is a well-known liver and kidney carcinogen in rodents and humans. The aim of the present study was to investigate the effect of FB1 on the proliferation and cell cycle of the normal human liver cell line HL-7702 and to explore the underlying molecular mechanisms of action. The cells were treated with FB1 (0.0, 0.1, 1.0, 10.0 and 100.0 µmol/l) for 24, 48, 72 and 96 h. Cell proliferation was assessed by colorimetric assay. Cell cycle analysis was performed by flow cytometry. The mRNA and protein expression of cyclin E and P21 were determined by RT‑PCR and western blot analysis, respectively. FB1 was initially demonstrated to significantly inhibit the proliferation of HL-7702 cells; however, cell proliferation increased with increasing treatment time. The percentage of cells in the G0/G1 phase was significantly increased by FB1; however, significantly decreased with an increasing concentration of FB1. The mRNA expression of cyclin E was upregulated and then gradually downregulated with increasing treatment time. The mRNA expression of P21 was significantly increased following treatment with 0.1 µmol/l FB1, and decreased following treatment with 10.0 and 100.0 µmol/l FB1 for different treatment durations. Western blot analysis showed that FB1 significantly increased the protein expression of cyclin E and significantly decreased the protein expression of P21 at various concentrations and treatment durations. Our results demonstrated that FB1 affects the cell cycle of normal human liver cells and that the underlying mechanism of action is associated with alterations in the expression levels of cyclin E and P21 induced by FB1.
authors.affiliation: Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Shao-Kang
authors.initials: SK
authors.lastname: Wang
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.forename: Li-Gang
authors.initials: LG
authors.lastname: Yang
authors.forename: Ruo-Fu
authors.initials: RF
authors.lastname: Shi
authors.forename: Gui-Ju
authors.initials: GJ
authors.lastname: Sun
mesh_terms: D002274:Carcinogens, Environmental / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D037341:Fumonisins / Q000633:toxicity*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002274:Carcinogens, Environmental; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D037341:Fumonisins; D012333:RNA, Messenger; C056933:fumonisin B1