title: Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells.
abstract: Given the previously described essential role for the p38 mitogen-activation protein kinase (p38 MAPK) signaling pathway in human hepatoma G2 cells (HepG2), we undertook the present study to investigate the role of the p38 MAPK signaling pathway in cell-cycle arrest induced by Furazolidone (FZD). The aim of this study was to determine the effects of FZD on HepG2 cells by activating and inhibiting the p38 MAPK signaling pathway. The cell cycle and proliferation of HepG2 cells treated with FZD were detected by flow cytometry and MTT assay in the presence or absence of p38 MAPK inhibitors (SB203580), respectively. Cyclin D1, cyclin D3 and CDK6 were detected by quantitative real-time PCR and western blot analysis. Our data showed that p38 MAPK became phosphorylated after stimulation with FZD. Activation of p38 MAPK could arise S-phase cell-cycle arrest and suppress cell proliferation. Simultaneously, inhibition of the p38 MAPK signaling pathway significantly prevented S-phase cell-cycle arrest, increased the percentage of cell viability and decreased the expression of cyclin D1, cyclin D3 and CDK6. These results demonstrated that FZD arose S-phase cell-cycle arrest via activating the p38 MAPK signaling pathway in HepG2 cells. Cyclin D1, cyclin D3 and CDK6 are target genes functioning at the downstream of p38 MAPK in HepG2 cells induced by FZD.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.forename: Chaoming
authors.initials: C
authors.lastname: Zhang
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhao
authors.forename: Xilong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000890:Anti-Infective Agents / Q000633:toxicity*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D005664:Furazolidone / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D018797:Cell Cycle Proteins; D005664:Furazolidone; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Furazolidone; S-phase cell-cycle arrest; cell proliferation; human hepatoma G2 cells; p38 MAPK