Clinical Cancer Research, Vol 4, Issue 10 2463-2471, Copyright © 1998 by American Association for Cancer Research

ARTICLES

Inhibition of human glioblastoma cell adhesion and invasion by 4-(4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3'-bromo-4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154)

RK Narla, XP Liu, D Klis and FM Uckun
Department of Experimental Oncology, and Wayne Hughes Institute, St. Paul, Minnesota 55113, USA.

Glioblastoma multiforme is a highly invasive primary brain tumor with a disappointingly high local recurrence rate and mortality despite intensive multimodality treatment programs. Therefore, new agents that are capable of inhibiting the infiltration of normal brain parenchyma by glioblastoma cells are urgently needed. Here, we show that the novel quinazoline derivatives 4-(4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3'-bromo-4'hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154) are potent inhibitors of glioblastoma cell adhesion and migration. Specifically, both compounds inhibited at micromolar concentrations: (a) integrin-mediated glioblastoma cell adhesion to the extracellular matrix proteins laminin, type IV collagen, and fibronectin; (b) integrin-independent epidermal growth factor-induced adhesion of glioblastoma cells to poly-L-lysine-coated tissue culture plates; (c) fetal bovine serum-induced polymerization of actin and actin stress fiber formation as well epidermal growth factor-stimulated formation of focal adhesion plaques in serum-starved glioblastoma cells; and most importantly, (d) glioblastoma cell migration in in vitro assays of tumor cell invasiveness using tumor cell spheroids and/or Matrigel-coated Boyden chambers. Further preclinical development of WHI-P131 and WHI-P154 may provide the basis for the design of more effective adjuvant chemotherapy programs for glioblastoma multiforme.

This article has been cited by other articles:

				P. C. De Witt Hamer, A. Jonker, S. Leenstra, J. M. Ruijter, and C. J.F. Van Noorden Quantification of Viability in Organotypic Multicellular Spheroids of Human Malignant Glioma using Lactate Dehydrogenase Activity: A Rapid and Reliable Automated Assay J. Histochem. Cytochem., January 1, 2005; 53(1): 23 - 34. [Abstract] [Full Text] [PDF]

				F. M. Uckun, J. Thoen, H. Chen, E. Sudbeck, C. Mao, R. Malaviya, X.-P. Liu, and C.-L. Chen CYP1A-Mediated Metabolism of the Janus Kinase-3 Inhibitor 4-(4'-Hydroxyphenyl)-amino-6,7-dimethoxyquinazoline: Structural Basis for Inactivation by Regioselective O-Demethylation Drug Metab. Dispos., January 1, 2002; 30(1): 74 - 85. [Abstract] [Full Text] [PDF]

				R. K. Narla, C.-L. Chen, Y. Dong, and F. M. Uckun In Vivo Antitumor Activity of Bis(4,7-dimethyl-1,10-phenanthroline) Sulfatooxovanadium(IV) {METVAN [VO(SO4)(Me2-Phen)2]} Clin. Cancer Res., July 1, 2001; 7(7): 2124 - 2133. [Abstract] [Full Text] [PDF]

				R. K. Narla, Y. Dong, D. Klis, and F. M. Uckun Bis(4,7-dimethyl-1,10-phenanthroline) Sulfatooxovanadium(IV) as a Novel Antileukemic Agent with Matrix Metalloproteinase Inhibitory Activity Clin. Cancer Res., April 1, 2001; 7(4): 1094 - 1101. [Abstract] [Full Text]