title: Antimetastatic activity of pinosylvin, a natural stilbenoid, is associated with the suppression of matrix metalloproteinases.
abstract: Metastasis is a major cause of death in cancer patients. Our previous studies showed that pinosylvin, a naturally occurring trans-stilbenoid mainly found in Pinus species, exhibited a potential cancer chemopreventive activity and also inhibited the growth of various human cancer cell lines via the regulation of cell cycle progression. In this study, we further evaluated the potential antimetastatic activity of pinosylvin in in vitro and in vivo models. Pinosylvin suppressed the expression of matrix metalloproteinase (MMP)-2, MMP-9 and membrane type 1-MMP in cultured human fibrosarcoma HT1080 cells. We also found that pinosylvin inhibited the migration of HT1080 cells in colony dispersion and wound healing assay systems. In in vivo spontaneous pulmonary metastasis model employing intravenously injected CT26 mouse colon cancer cells in Balb/c mice, pinosylvin (10 mg/kg body weight, intraperitoneal administration) significantly inhibited the formation of tumor nodules and tumor weight in lung tissues. The analysis of tumor in lung tissues indicated that the antimetastatic effect of pinosylvin coincided with the down-regulation of MMP-9 and cyclooxygenase-2 expression, and phosphorylation of ERK1/2 and Akt. These data suggest that pinosylvin might be an effective inhibitor of tumor cell metastasis via modulation of MMPs.
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Hyen Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Yoonho
authors.initials: Y
authors.lastname: Shin
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Min
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hong
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Yong-Hyun
authors.initials: YH
authors.lastname: Ahn
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Pyee
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D020935:MAP Kinase Signaling System; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010766:Phosphorylation; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D000094162:Phytoalexins
chemical_list: D000970:Antineoplastic Agents; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D013267:Stilbenes; C049032:pinosylvin; D000094162:Phytoalexins