title: Induction of nucleolin translocation by acharan sulfate in A549 human lung adenocarcinoma.
abstract: Acharan sulfate (AS), isolated from the giant African snail Achatina fulica, is a novel glycosaminoglycan, consisting primarily of the repeating disaccharide structure alpha-D-N-acetylglucosaminyl (1 --> 4) 2-sulfoiduronic acid. AS shows anti-tumor activity in vitro and in vivo. Despite this activity, AS is only weakly cytotoxic towards cancer cells. We examine the interactions between AS and cell-surface proteins in an effort to explain this anti-tumor activity. Using flow cytometry and affinity column chromatography, we confirm that AS has strong affinity to specific cell-surface proteins including nucleolin (NL) in A549 human lung adenocarcinomas. Surprisingly, we found the translocation of NL from nucleus to cytoplasm under the stimulation of AS (100 microg/ml) in vitro. Also, as NL exits the nucleus, the levels of growth factors such as bFGF and signaling cascade proteins, such as p38, p53, and pERK, are altered. These results suggest that the communication between AS and NL plays a critical role on signal transduction in tumor inhibition.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Joo
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Youmie
authors.initials: Y
authors.lastname: Park
authors.forename: Nam Young
authors.initials: NY
authors.lastname: Park
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002846:Chromatography, Affinity; D003593:Cytoplasm / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012908:Snails / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097796:Nucleolin
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D016222:Fibroblast Growth Factor 2; D006025:Glycosaminoglycans; D008565:Membrane Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; D000097796:Nucleolin; C106771:acharan sulfate