Induction of nucleolin translocation by acharan sulfate in A549 human lung adenocarcinoma.
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.
Joo
Eun Ji
EJ
Natural Products Research Institute, College of Pharmacy, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, Korea.
Yang
Hui
H
Park
Youmie
Y
Park
Nam Young
NY
Toida
Toshihiko
T
Linhardt
Robert J
RJ
Kim
Yeong Shik
YS
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
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