title: Novel heparan sulfate mimetic compounds as antitumor agents.
abstract: Heparan sulfate glycosaminoglycans (HSGAGs) are involved in tumor cell growth, adhesion, invasion, and migration, due to their interactions with various proteins. In this study, novel HSGAG-mimetic compounds (KI compounds) were designed and synthesized. As a result of cell-based assays, KI-105 was found to exert potent inhibitory activities against migration and invasion of human fibrosarcoma HT1080 cells. The present results indicate that a novel invasion/migration inhibitor, KI-105, can increase the adherence of HT1080 cells. It was conceivable that this cellular effect was caused by an increase in the amount of cell-surface HSGAGs and focal adhesions. Although further investigations are needed to decipher the molecular mechanism of KI-105, it is suggested that heparanase and Cdc42 are involved in its biological effects.
authors.affiliation: Antibiotics Laboratory, RIKEN Discovery Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishida
authors.forename: Michal K
authors.initials: MK
authors.lastname: Wierzba
authors.forename: Takayuki
authors.initials: T
authors.lastname: Teruya
authors.forename: Siro
authors.initials: S
authors.lastname: Simizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015195:Drug Design; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010641:Phenotype; D013329:Structure-Activity Relationship; D000099175:Heparanase
chemical_list: D000970:Antineoplastic Agents; D005966:Glucuronidase; D006497:Heparan Sulfate; D000099175:Heparanase