A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines

BMC Complementary and Alternative Medicine

Research Article

Wolfram Trowitzsch-Kienast¹  Rajan Somasundaram²  Ulrike Erben²  Martin Zeitz²  Thorsten Stroh²  Martin Ruehl²  Christian Freise²  Daniel Seehofer³  Ulf Neumann⁴  Ki Young Kim⁵ 

[1] Department of Chemical and Pharmaceutical Engineering, Beuth Hochschule für Technik, Luxemburger Str. 10, 13353, Berlin, Germany;Department of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany;Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany;Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany;Department of Surgery, University Hospital Aachen, Pauwelstraße 30, 52074, Aachen, Germany;Faculty of Beauty Design, Human Environmental Science College, Wonkwang University, Iksan City, South Korea;

关键词: Vascular Endothelial Growth Factor;    Sorafenib;    Vascular Endothelial Growth Factor Expression;    Hepatic Stellate Cell;    Hep3B Cell;   

DOI  :  10.1186/1472-6882-11-39

 received in 2011-01-24, accepted in 2011-05-12,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundIn traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush Lindera obtusiloba (L.obtusiloba) is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of L.obtusiloba extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of L.obtusiloba extract on human hepatocellular carcinoma (HCC) cell lines and the signaling pathways involved.MethodsFour human HCC cell lines representing diverse stages of differentiation were treated with L.obtusiloba extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined.ResultsL.obtusiloba extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, L.obtusiloba extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase.ConclusionsThe traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized L.obtusiloba extract should be further analysed for its active compounds and explored as (complementary) treatment option for HCC.

【 授权许可】

Unknown   
© Freise et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.