title: Comparison of the cytotoxic impact of chlorfluazuron on selected insect and human cell lines.
abstract: To gain new insight into the mechanism of selective cytotoxicity of benzoylureas as insecticides, the in vitro mode of action of chlorfluazuron was investigated on lepidopteran Tn5B1-4 and Sf-21 cells and human Hek293 and HepG2 cells. Chlorfluazuron inhibited the proliferation of Tn5B1-4 and Sf-21 cells with 50% inhibitory concentration values (IC50) of 4.96 µM and 1.12 µM at 48 h and 2.37 µM and 1.76 µM at 96 h, respectively, versus that of Hek293 and HepG2 cells with IC50 values >20 µM. When transferred to chlorfluazuron-free medium, lepidopteran Tn5B1-4 and Sf-21 cells had a postinhibitory recovery development period within 24 h followed by a suppressed increase in cell viability, but human Hek293 and HepG2 cells showed an accelerated increase over their control level. Chlorfluazuron affected Tn5B1-4 and Sf-21 cells, with ≥1.8-fold decreases in the ratio of cellular N-acetylglucosamine (GlcNAc) level and protein content and ≥1.5-fold increases in the mitotic index and G2 /M-phase arrest. Neither Hek293 nor HepG2 cells contained GlcNAc, and chlorfluazuron had no significant effects on the cell cycle and mitotic index of Hek293 and HepG2 cells. In conclusion, the differences between human and lepidopteran cell lines in the characteristic GlcNAc content, G2 /M arrest in the cycle progress, and mitotic index of cells in response to chlorfluazuron may contribute to the selective toxicity of chlorfluazuron to lepidopteran cells.
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Miaoqing
authors.initials: M
authors.lastname: Lu
authors.affiliation: Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Liming
authors.initials: L
authors.lastname: Tao
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007915:Lepidoptera / Q000166:cytology / Q000187:drug effects; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D010671:Phenylurea Compounds / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*
chemical_list: D010671:Phenylurea Compounds; D011725:Pyridines; C057223:chlorfluazuron; D000117:Acetylglucosamine
keywords: Chlorfluazuron; Cytotoxicity; Hek293; HepG2; Sf-21; Tn5B1-4