title: (+)-Episesamin exerts anti-neoplastic effects in human hepatocellular carcinoma cell lines via suppression of nuclear factor-kappa B and inhibition of MMP-9.
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 NF-ĸB - offer a promising therapeutic approach. Aim of this study was to examine anti-neoplastic effects of (+)-episesamin which has been isolated from an anti-fibrotic extract of Lindera obtusiloba on human HCC cells with particular interest in activation of NF-κB. The human HCC cell lines HepG2, Huh-7 and SK-Hep1 were treated with (+)-episesamin. Beside measurement of proliferation, invasion and apoptosis, effects of (+)-episesamin on NF-κB-activity, VEGF secretion and enzymatic MMP-9 activity were determined. Anti-inflammatory effects were assessed by IL-6 ELISA using HCC cells and RAW264.7 macrophages. 10 μM (+)-episesamin reduced the proliferation of HCC cells by ~50%, suppressed invasion and induced apoptosis. DNA-binding ELISA experiments revealed that (+)-episesamin treated HCC cells showed a suppressed basal and TNFα-induced activation of NF-κB and a subsequent suppression of TNFα- and LPS-induced IL-6 production. Further, (+)-episesamin exhibited inhibitory effects on the enzymatic activity of recombinant MMP-9 and the secretion of MMP-9 and VEGF by HCC cells into their supernatants. Our findings show that anti-neoplastic effects of (+)-episesamin are mediated via suppressed activation of NF-κB which entails a decreased release of pro-inflammatory IL-6. In addition, (+)-episesamin inhibits MMP-9, 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.
authors: Department of Gastroenterology, Infectiology and Rheumatology, Charité - Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
authors: Christian
authors: C
authors: Freise
authors: Wolfram
authors: W
authors: Trowitzsch-Kienast
authors: Martin
authors: M
authors: Ruehl
authors: Ulrike
authors: U
authors: Erben
authors: Daniel
authors: D
authors: Seehofer
authors: Ki Young
authors: KY
authors: Kim
authors: Martin
authors: M
authors: Zeitz
authors: Rajan
authors: R
authors: Somasundaram
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D004149:Dioxoles; D015850:Interleukin-6; D017705:Lignans; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9; C054125:sesamin