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Back to 2015 Annual Meeting Program Suppressive Effects of Luteolin on Extracellular Matrix Protein Expression in Activated Hepatic Stellate Cells Xiao-Fu Wang1, Arline J. Kandathiparampil1, Fredrick Bohanon1, Winston F. Crowell1, Cristiana Rastellini1, Jia Zhou2, Ravi Radhakrishnan*1 1Surgery, University of Texas Medical Branch, Galveston, TX; 2Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX Luteolin belongs to the flavonoid family, and is present in many fruits and vegetables. Luteolin is found to have anti-tumorigenic, anti-oxidant, and anti-inflammatory properties. Recent studies have identified the therapeutic effect of luteolin on a mouse model of liver fibrosis; however, its effects on extracellular matrix (ECM) proteins remain largely unknown. Here, we investigated the effects of luteolin on activated hepatic stellate cells (HSC), the major source for excessive ECMs deposition in hepatic fibrosis. Methods. Alamar Blue Assay was used for proliferation analysis of rat activated HSC cell line HSC-T6. Cellular proteins were measured by immunoblot. Apoptosis was determined with the staining of Yo-Pro-1 and propidium iodide. Cell cycle was assessed by flow cytometry. Results. Luteolin treatment induced HSC-T6 cells apoptosis and potent growth inhibition in a dose-dependent fashion. Luteolin induced G1 phases cell cycle arrest, and was correlated with increased p53 activity, and decreased expression of cyclinD1, cyclinB1, and CDK4. Importantly, the HSC activation marker α-smooth muscle actin, as well as major ECM proteins collagen type I and fibronectin (FN) were markedly down-regulated by luteolin in a time-and dose-dependent manner. Protein stability study with cycloheximide, revealed that luteolin significantly accelerated the decline of collagen type I protein in HSC. TGF-β is a major profibrogenic cytokine. We found that pretreatment of luteolin blocked TGF-β-induced collagen type I, FN, Smad2/3 phosphorylation and nuclear translocation. Conclusion. Luteolin treatment inhibited HSC proliferation, suppressed endogenous and TGF-β-induced ECMs expression, while impairing TGF-β signaling in HSC cells. Luteolin may be a promising agent for reducing liver fibrosis. Back to 2015 Annual Meeting Program |
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