title: Ankaflavin and Monascin Induce Apoptosis in Activated Hepatic Stellate Cells through Suppression of the Akt/NF-κB/p38 Signaling Pathway.
abstract: The increased proliferation of activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and excessive extracellular matrix (ECM)-protein production. We examined the inhibitory effects of the Monascus purpureus-fermented metabolites, ankaflavin and monascin (15 and 30 μM), on the Akt/nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) signaling pathways in HSC-T6 (activated hepatic stellate cell line). Ankaflavin and monascin (30 μM) induced apoptosis and significantly inhibited cell growth (cell viabilities: 80.2 ± 5.43% and 62.8 ± 8.20%, respectively, versus control cells; P < 0.05). Apoptosis and G1 phase arrest (G1 phase percentages: 76.1 ± 2.85% and 79.9 ± 1.80%, respectively, versus control cells 65.9 ± 4.94%; P < 0.05) correlated with increased p53 and p21 levels and caspase 3 activity and decreased cyclin D1 and Bcl-2-family protein levels (P < 0.05, all cases). The apoptotic effects of ankaflavin and monascin were HSC-T6-specific, suggesting their potential in treating liver fibrosis.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University , No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.
authors.forename: Chih-Fu
authors.initials: CF
authors.lastname: Cheng
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University , No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005415:Flavins / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D032741:Monascus / Q000737:chemistry*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D005415:Flavins; D006575:Heterocyclic Compounds, 3-Ring; D016328:NF-kappa B; D010936:Plant Extracts; C499916:ankaflavin; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C517880:monascin
keywords: Monascus purpureus; ankaflavin; apoptosis; liver fibrosis; monascin