TY - JOUR
T1 - Novel heparan sulfate mimetic compounds as antitumor agents
AU - Ishida, Keisuke
AU - Wierzba, Michal K.
AU - Teruya, Takayuki
AU - Simizu, Siro
AU - Osada, Hiroyuki
N1 - Funding Information:
The authors would like to thank T. Yamazaki and S. Miyasaka (Taiho Pharmaceutical Co., Ltd.) for the database search and spectral measurements, respectively. This study was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports, Culture and Technology of Japan, and the Chemical Biology Project (RIKEN).
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/1942524289
UR - https://www.scopus.com/pages/publications/1942524289#tab=citedBy
U2 - 10.1016/j.chembiol.2004.02.015
DO - 10.1016/j.chembiol.2004.02.015
M3 - Article
C2 - 15123266
AN - SCOPUS:1942524289
SN - 1074-5521
VL - 11
SP - 367
EP - 377
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 3
ER -