title: Tricin inhibits proliferation of human hepatic stellate cells in vitro by blocking tyrosine phosphorylation of PDGF receptor and its signaling pathways.
abstract: 4',5,7-Trihydroxy-3',5'-dimethoxyflavone (Tricin), a naturally occurring flavone, has anti-inflammatory potential and exhibits diverse biological activities including antigrowth activity in several human cancer cell lines and cancer chemopreventive effects in the gastrointestinal tract of mice. The present study aimed to investigate the biological actions of tricin on hepatic stellate cells (HSCs) in vitro, exploring its potential as a treatment of liver fibrosis, since HSC proliferation is closely related to the progression of hepatic fibrogenesis in chronic liver diseases leading to irreversible liver cirrhosis and hepatocellular carcinoma. Tricin inhibited platelet-derived growth factor (PDGF)-BB-induced cell proliferation by blocking cell cycle progression and cell migration in the human HSC line LI90 and culture-activated HSCs. It also reduced the phosphorylation of PDGF receptor β and the downstream signaling molecules ERK1/2 and Akt, which might be due to its tyrosine kinase inhibitor properties rather than inhibition of the direct binding between PDGF-BB and its receptor. Our findings suggest that tricin might be beneficial in HSC-targeting therapeutic or chemopreventive applications for hepatic fibrosis.
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan. seki_naoko@kurume-u.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Seki
authors.forename: Uhi
authors.initials: U
authors.lastname: Toh
authors.forename: Koji
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
authors.forename: Kunitomo
authors.initials: K
authors.lastname: Watanabe
authors.forename: Masatora
authors.initials: M
authors.lastname: Aoki
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Anna
authors.initials: A
authors.lastname: Nakamura
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.forename: Jingo
authors.initials: J
authors.lastname: Kusukawa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamana
mesh_terms: D000077214:Becaplermin; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C017769:tricin; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3