title: Antimetastatic effects of gambogic acid are mediated via the actin cytoskeleton and NF-κB pathways in SK-HEP1 cells.
abstract: Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers with a high metastatic potential. The prevention of HCC metastasis is a critical target for effective therapies in HCC. Gambogic acid (GA), a natural compound obtained from Garcinia hanburyi has reported anticancer activity in cell lines. However, the antimetastatic mechanisms of GA are unclear, particularly with respect to HCC. In this study, the influence of GA on migration and invasion of SK-HEP1 cells was evaluated. At concentrations above 0.6 μM, GA reduced cell proliferation in SK-HEP1 cells without affecting proliferation of noncancerous HEK-293 cells. GA also suppressed migration and invasion of SK-HEP1 cells. GA downregulated the expression of the integrin β1/rho family GTPase signaling pathway, suppressed the actin rearrangement related to cell cytoskeleton and migration and decreased matrix metalloproteinases MMP-2, MMP-9, and NF-κB expression involved in cancer invasion. These results suggest that GA may be a potential lead in developing an antimetastatic therapeutic for the treatment of HCC.
authors.affiliation: Department of Microbiology, College of Natural Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Min-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Natural Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Nan-Hee
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Natural Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Kang
authors.affiliation: Department of Marine Biology, College of Fishery Sciences, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Chul-Woong
authors.initials: CW
authors.lastname: Oh
authors.affiliation: Department of Microbiology, College of Natural Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Gun-Do
authors.initials: GD
authors.lastname: Kim
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D044004:Xanthones; C052659:gambogic acid
keywords: NF-κB; actin cytoskeleton; gambogic acid; hepatocellular carcinoma; metastasis