Suppression of AMF/PGI-mediated tumorigenic activities by ursolic acid in cultured hepatoma cells and in a mouse model.

in Sciences Citation Index(SCI), 科學引文索引資料庫(SCI)
標題Suppression of AMF/PGI-mediated tumorigenic activities by ursolic acid in cultured hepatoma cells and in a mouse model.
出版類型SCI(Sciences Citation Index)
AuthorsWen-Ling Shih, 施玟玲, Feng-Ling Yu 余風鈴, CHING-DONG CHANG 張清棟, Liao Ming-Huei 廖明輝, Wu Hung-Yi 吳弘毅, & Ping-Yuan Lin 林炳源
出版日期2013 / 10

Our previous studies demonstrated that autocrine motility factor/phosphoglucose isomerase (AMF/PGI) possesses tumorigenic activities through the modulation of intracellular signaling. We then investigated the effects of ursolic acid (UA), oleanolic acid (OA), tangeretin, and nobiletin against AMF/PGI-mediated oncogenesis in cultured stable Huh7 and Hep3B cells expressing wild-type or mutated AMF/PGI and in a mouse model in this study. The working concentrations of the tested compounds were lower than their IC10, which was determined by Brdu incorporation and colony formation assay. Only UA efficiently suppressed the AMF/PGI-induced Huh7 cell migration and MMP-3 secretion. Additionally, UA inhibited the AMF/PGI-mediated protection against TGF-β-induced apoptosis in Hep3B cells, whereas OA, tangeretin, and nobiletin had no effect. In Huh7 cells and tumor tissues, UA disrupted the Src/RhoA/PI 3-kinase signaling and complex formation induced by AMF/PGI. In the Hep3B system, UA dramatically suppressed AMF/PGI-induced anti-apoptotic signaling transmission, including Akt, p85, Bad, and Stat3 phosphorylation. AMF/PGI enhances tumor growth, angiogenesis, and pulmonary metastasis in mice, which is correlated with its enzymatic activity, and critically, UA intraperitoneal injection reduces the tumorigenesis in vivo, enhances apoptosis in tumor tissues and also prolongs mouse survival. Combination of sub-optimal dose of UA and cisplatin, a synergistic tumor cell-killing effects was found. Thus, UA modulates intracellular signaling and might serve as a functional natural compound for preventing or alleviating hepatocellular carcinoma.

期刊名稱Molecular Carcinogenesis
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