title: Anti-fibrotic and anti-tumorigenic effects of rhein, a natural anthraquinone derivative, in mammalian stellate and carcinoma cells.
abstract: Anthraquinone compounds have been recognized to possess antiinflammatory, anti-fibrotic and anti-tumour properties and thus applied in human and veterinary therapeutics as active substances of medicinal products. Amongst the anthraquinones isolated from Rheum palmatum, also known as da-huang, rhein was detected as one of the highest metabolite contents in the bloodstream of mammals. The biological activities of rhein therefore deserve detailed investigation. In this study, we aimed to delineate the mechanism of inhibitory actions of rhein on fibrotic and tumorigenic processes by means of various biochemical assays, such as immunofluorescent staining, real-time polymerase chain reaction (PCR) and western blotting analyses in rat pancreatic stellate cells (LTC-14), human pancreatic ductal adenocarcinoma cells (PANC-1) and human colon carcinoma cells (SW480 and SW620). Our results demonstrated that the application of rhein notably suppressed the mRNA and protein levels of various fibrotic and tumorigenic mediators including alpha-smooth muscle actin, type I collagen, fibronectin, N-cadherin and matrix metalloproteinases in the testing mammalian cells. The mechanism of the suppressive actions of rhein was associated with the modulation of the sonic hedgehog and serine-threonine kinase signalling pathways. In conclusion, we suggest that rhein may serve as a therapeutic or an adjuvant agent in anti-fibrotic and anti-tumorigenic approaches.
authors.affiliation: Cancer and inflammation Center, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong.
authors.forename: Siu Wai
authors.initials: SW
authors.lastname: Tsang
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Bian
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D058954:Pancreatic Stellate Cells / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D012250:Rheum / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D024042:Collagen Type I; D005353:Fibronectins; D053823:Hedgehog Proteins; D017346:Protein Serine-Threonine Kinases; D020782:Matrix Metalloproteinases; C020491:rhein
keywords: anthraquinone; anti-fibrotic agent; anti-tumour agent; carcinoma cells; rhein; stellate cells