title: Opposite effects of JNK and p38 MAPK signaling pathways on furazolidone-stimulated S phase cell cycle arrest of human hepatoblastoma cell line.
abstract: Furazolidone (FZD), a synthetic nitrofuran with a broad spectrum of antimicrobial actions, is known to induce genotoxicity and potential carcinogenicity in several types of cells, but little is known about its p38 mitogen-activation protein kinase (p38 MAPK) and c-Jun N-terminal protein kinase (JNK) pathways in human hepatoblastoma cell line (HepG2). Given the previously described essential roles of p38 MAPK and JNK pathways in HepG2 cells, we undertook the present study to investigate the roles of p38 MAPK and JNK pathways in cell cycle arrest of HepG2 cells stimulated with FZD. Here we reported that FZD could obviously induce S phase cell cycle arrest, suppress cell growth, increase the activity of phosphorylated p38 (p-p38), and decrease the activity of phosphorylated JNK (p-JNK) in HepG2 cells. Simultaneously, inhibition of p38 MAPK pathway could significantly reduce FZD-stimulated S phase cell cycle arrest, active cell growth, decrease the activity of p-p38, and increase the activity of p-JNK. To the opposite, inhibition of JNK pathway could significantly increase FZD-stimulated S phase cell cycle arrest, suppress cell growth, decrease the activity of p-JNK, and increase the activity of p-p38. These results demonstrate that JNK and p38 MAPK pathways have opposite roles in FZD-stimulated S phase cell cycle arrest of HepG2 cells. FZD induces S phase cell cycle arrest and suppresses cell proliferation of HepG2 cells via activating the pathway from p38 to p-p38 and inhibiting the pathway from JNK to p-JNK.
authors: Department of Pharmacology and Toxicology, China Agricultural University, Beijing, People's Republic of China.
authors: Yu
authors: Y
authors: Sun
authors: Shusheng
authors: S
authors: Tang
authors: Xi
authors: X
authors: Jin
authors: Chaoming
authors: C
authors: Zhang
authors: Wenxia
authors: W
authors: Zhao
authors: Xilong
authors: X
authors: Xiao
mesh_terms: D000994:Antitrichomonal Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005664:Furazolidone / Q000494:pharmacology*; D018197:Hepatoblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D016196:S Phase / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000994:Antitrichomonal Agents; D005664:Furazolidone; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: Cell growth suppression; Furazolidone; HepG2 cells; JNK; S phase cell cycle arrest; p38 MAPK