title: Dextran sulfate suppresses cell adhesion and cell cycle progression of melanoma cells.
abstract: We have reported that dextran sulfate is a possible candidate for an antimetastatic drug because it inhibits cell adhesion. It has been demonstrated that dextran sulfate can detach cancer cells adhering to the bottom of plastic flasks, and that the detached cells do not readhere or proliferate. In this study, we investigated the effects of dextran sulfate on cancer cells, focusing on cell cycle regulators as well as cell adhesion molecules. The effects of dextran sulfate on the cell cycle were examined by flow cytometry, and changes in gene expression caused by dextran sulfate were analyzed by cDNA microarray to identify changes in adhesion and cell cycle genes. By flow cytometry, treatment with dextran sulfate increased the percentage of cells in the G1/G0-phase, and decreased those in the S- and G2/M-phases. Analysis by cDNA microarray revealed decreased expression of several genes essential for progression of the G1- and S-phases. The expression of the adhesion factors involved in metastases was also suppressed. Furthermore, we confirmed these changes in the gene expression by Northern and Western blotting. Our results indicate that dextran sulfate suppresses cell adhesion and cell cycle progression, both of which are essential for metastasis, suggesting that dextran sulfate could be used as an antimetastatic agent.
authors.affiliation: Department of Digestive Surgery, Kyoto Prefecture University of Medicine, Kamigyo-ku, Kawaramachi-dori, Kyoto 602-8566, Japan. nao3@d2.dion.ne.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takagi
authors.forename: Chouhei
authors.initials: C
authors.lastname: Sakakura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kin
authors.forename: Yuen
authors.initials: Y
authors.lastname: Nakase
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Fukuda
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shimomura
authors.forename: Tadao
authors.initials: T
authors.lastname: Ito
authors.forename: Junshin
authors.initials: J
authors.lastname: Fujiyama
authors.forename: Junya
authors.initials: J
authors.lastname: Yamasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
authors.forename: Akeo
authors.initials: A
authors.lastname: Hagiwara
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D016264:Dextran Sulfate / Q000494:pharmacology*; D005434:Flow Cytometry; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D016264:Dextran Sulfate