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: Chih-Fu Cheng, Tzu-Ming Pan
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 64 Issue 49 Pg. 9326-9334 (Dec 14 2016) ISSN: 1520-5118 [Electronic] United States
• PMID: 27960292 (Publication Type: Journal Article)

Chemical References

• Flavins
• Heterocyclic Compounds, 3-Ring
• NF-kappa B
• Plant Extracts
• ankaflavin
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• monascin

Topics

• Animals
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Down-Regulation (drug effects)
• Flavins (pharmacology)
• Hepatic Stellate Cells (cytology, drug effects, metabolism)
• Heterocyclic Compounds, 3-Ring (pharmacology)
• Humans
• Liver Cirrhosis (drug therapy, genetics, metabolism, physiopathology)
• Male
• Monascus (chemistry)
• NF-kappa B (genetics, metabolism)
• Plant Extracts (pharmacology)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Rats
• Signal Transduction (drug effects)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)