Dextran sulfate suppresses cell adhesion and cell cycle progression of melanoma cells.
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.
Takagi
Tsuyoshi
T
Department of Digestive Surgery, Kyoto Prefecture University of Medicine, Kamigyo-ku, Kawaramachi-dori, Kyoto 602-8566, Japan. nao3@d2.dion.ne.jp
Sakakura
Chouhei
C
Kin
Shuichi
S
Nakase
Yuen
Y
Fukuda
Kenichiro
K
Shimomura
Katsumi
K
Ito
Tadao
T
Fujiyama
Junshin
J
Yamasaki
Junya
J
Tsujimoto
Hiroyuki
H
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Yamagishi
Hisakazu
H
Hagiwara
Akeo
A
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
D016264:Dextran Sulfate