Chemistry & Biology 2004-03-01

Novel heparan sulfate mimetic compounds as antitumor agents.

Keisuke Ishida, Michal K Wierzba, Takayuki Teruya, Siro Simizu, Hiroyuki Osada

文献索引：Chem. Biol. 11(3) , 367-77, (2004)

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摘要

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.