MAZ51, an indolinone that inhibits endothelial cell and tumor cell growth in vitro, suppresses tumor growth in vivo

Vladimir Kirkin; Wilko Thiele; Petra Baumann; Ralph Mazitschek; Katrin Rohde; Guido Fellbrich; Herbert Weich; Johannes Waltenberger; Athanassios Giannis; Jonathan P Sleeman

doi:10.1002/ijc.20509

MAZ51, an indolinone that inhibits endothelial cell and tumor cell growth in vitro, suppresses tumor growth in vivo

Int J Cancer. 2004 Dec 20;112(6):986-93. doi: 10.1002/ijc.20509.

Authors

Vladimir Kirkin¹, Wilko Thiele, Petra Baumann, Ralph Mazitschek, Katrin Rohde, Guido Fellbrich, Herbert Weich, Johannes Waltenberger, Athanassios Giannis, Jonathan P Sleeman

Affiliation

¹ Forschungszentrum Karlsruhe, Institut für Toxikologie und Genetik, Karlsruhe, Germany.

PMID: 15386354
DOI: 10.1002/ijc.20509

Abstract

We have recently described MAZ51, an indolinone that blocks the ligand-induced autophosphorylation of VEGFR-3, a receptor tyrosine kinase that plays a central role in the regulation of lymphangiogenesis. Here we show that MAZ51 is able to block the proliferation of VEGFR-3-expressing human endothelial cells and is less potently able to induce their apoptosis. MAZ51 also inhibits the proliferation and induces the apoptosis of a variety of non-VEGFR-3-expressing tumor cell lines. These data suggest that MAZ51 blocks the activity of tyrosine kinases in addition to VEGFR-3. In vivo, MAZ51 significantly inhibits the growth of rat mammary carcinomas. These data establish MAZ51 as a compound with antitumor properties that inhibits tumor growth directly and also indirectly by interfering with tumor-host interactions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
DNA, Neoplasm / analysis
Endothelial Cells / drug effects*
Endothelial Cells / metabolism*
Enzyme-Linked Immunosorbent Assay
Female
Humans
Indoles / pharmacology*
Lymphangiogenesis / drug effects
Mammary Neoplasms, Experimental / drug therapy
Naphthalenes / pharmacology*
Phosphorylation
Protein-Tyrosine Kinases / antagonists & inhibitors*
Rats
Rats, Wistar
Receptor, IGF Type 1 / drug effects
Receptor, IGF Type 1 / metabolism
Receptor, Platelet-Derived Growth Factor beta / drug effects
Receptor, Platelet-Derived Growth Factor beta / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Vascular Endothelial Growth Factor Receptor-3 / antagonists & inhibitors*

Substances

3-(4-dimethylamino-naphthalen-1-ylmethylene)-1,3-dihydro-indol-2-one
Antineoplastic Agents
DNA, Neoplasm
Indoles
Naphthalenes
Protein-Tyrosine Kinases
Receptor, IGF Type 1
Receptor, Platelet-Derived Growth Factor beta
Vascular Endothelial Growth Factor Receptor-3