+Episesamin exerts antineoplastic effects in h

Authors: Christian Freise Wolfram TrowitzschKienast Martin Ruehl Ulrike Erben Daniel Seehofer Ki Young Kim Martin Zeitz Rajan Somasundaram

Publish Date: 2011/11/03

Volume: 30, Issue: 6, Pages: 2087-2095

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Abstract

Hepatocellular carcinoma HCC is one of the most common malignancies worldwide Treatment options especially in advanced tumor stages are still limited Inhibition of signaling cascades involved in the pathogenesis of HCC such as NFĸB offer a promising therapeutic approach Aim of this study was to examine antineoplastic effects of +episesamin which has been isolated from an antifibrotic extract of Lindera obtusiloba on human HCC cells with particular interest in activation of NFκB The human HCC cell lines HepG2 Huh7 and SKHep1 were treated with +episesamin Beside measurement of proliferation invasion and apoptosis effects of +episesamin on NFκBactivity VEGF secretion and enzymatic MMP9 activity were determined Antiinflammatory effects were assessed by IL6 ELISA using HCC cells and RAW2647 macrophages 10 μM +episesamin reduced the proliferation of HCC cells by ~50 suppressed invasion and induced apoptosis DNAbinding ELISA experiments revealed that +episesamin treated HCC cells showed a suppressed basal and TNFαinduced activation of NFκB and a subsequent suppression of TNFα and LPSinduced IL6 production Further +episesamin exhibited inhibitory effects on the enzymatic activity of recombinant MMP9 and the secretion of MMP9 and VEGF by HCC cells into their supernatants Our findings show that antineoplastic effects of +episesamin are mediated via suppressed activation of NFκB which entails a decreased release of proinflammatory IL6 In addition +episesamin inhibits MMP9 which is strongly expressed in invasive HCC and the production of proangiogenic VEGF We conclude that +episesamin has the potential to be further explored as a complementary treatment for HCC

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