Gabexate mesilate inhibits colon cancer growth, invasion, and metastasis by reducing matrix metalloproteinases and angiogenesis

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Wan-Hee YoonYoung S Kim

Abstract

Gabexate mesilate (GM), a synthetic protease inhibitor, has an antiproteinase activity on various types of plasma serine proteases. However, its role on matrix metalloproteinases (MMPs) has not been identified. In this study, we investigated the effect of GM on MMPs and on the invasion and metastasis of human colon cancer cell lines and neoangiogenesis. The activities of MMPs secreted from these cells were significantly reduced by GM but unaffected by the serine protease inhibitor aprotinin. GM directly inhibited purified progelatinase A derived from T98G human glioblastoma cells. In vitro, GM significantly reduced the invasive ability of colon cancer cells but not cellular motility, whereas aprotinin affected neither. Liver metastatic ability and tumorigenic potential in nude mice were remarkably reduced on treatment with GM. Immunohistochemical analysis of GM-treated tumors in mice showed a marked increase in apoptosis and a significant reduction in tumor angiogenesis. Human umbilical vein endothelial cell proliferation, tube formation, and neoangiogenesis in the rabbit cornea and Matrigel implanted in mice were significantly inhibited by GM. These results suggest that GM is a novel inhibitor of MMPs and that it may inhibit t...Continue Reading

References

Oct 13, 1977·Biochimica Et Biophysica Acta·Y TamuraS Fujii
Jun 5, 1991·Journal of the National Cancer Institute·A AlbiniW G Stetler-Stevenson
Jan 23, 1987·Science·J Folkman, M Klagsbrun
Jan 1, 1985·Advances in Cancer Research·K DanøL Skriver
Nov 1, 1993·Journal of Cellular Physiology·A N MurphyW G Stetler-Stevenson
Aug 1, 1994·International Journal of Cancer. Journal International Du Cancer·R G ChiriviR Giavazzi
Sep 1, 1994·International Journal of Cancer. Journal International Du Cancer·K NaitoA Okuyama
Dec 1, 1993·Journal of Cellular Physiology·S DesrivièresS Ménashi
May 24, 1996·Biochemical and Biophysical Research Communications·W H YoonB D Hwang
Dec 17, 1998·Trends in Cell Biology·M E Lukashev, Z Werb
May 4, 1999·The Journal of Clinical Investigation·W G Stetler-Stevenson
Aug 26, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S Curran, G I Murray
Jul 14, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·M S Pepper

❮ Previous
Next ❯

Citations

Jul 23, 2008·Nucleic Acids Research·Chae-Ok YunJin-Soo Kim
Jun 15, 2010·Experimental & Molecular Medicine·Jung-Wook KimYong Song Gho
Oct 9, 2014·BioMed Research International·Michele AmmendolaGirolamo Ranieri
Mar 1, 2006·Expert Opinion on Biological Therapy·Tamara T LahCornelis J F Van Noorden
Mar 6, 2007·Auris, Nasus, Larynx·Yukiko YamashitaMamoru Tsukuda
Nov 1, 2016·Archivum Immunologiae Et Therapiae Experimentalis·Anca Maria Cimpean, Marius Raica
Dec 22, 2017·International Journal of Molecular Sciences·Min-Hua WuYi-Hsien Hsieh
Dec 4, 2014·World Journal of Gastroenterology : WJG·Hsi-Hsien HsuChih-Yang Huang
Oct 3, 2018·Biological & Pharmaceutical Bulletin·HyeongSeob KwakSang-Han Lee
May 28, 2020·International Journal of Molecular Sciences·Eva AndreuzziMaurizio Mongiat
Oct 4, 2014·International Journal of Immunopathology and Pharmacology·R ImbertiM Vairetti
Jun 8, 2017·International Journal of Molecular Sciences·Hsi-Hsien HsuChih-Yang Huang
Sep 6, 2020·International Journal of Molecular Sciences·Min-Hua WuTsung-Ho Ying
Nov 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jong-Seok KimByung-Doo Hwang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis