Antiangiogenic Effects of the Quinoline-3-Carboxamide Linomide

Jasminka Vukanovic, John T. Isaacs

Research output: Contribution to journalArticlepeer-review

Abstract

Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1 -methyl-2-oxoqui-noline-3-carboxamide) has a reproducible in vivo antitumor effect against a series of both androgen responsive and independent Dunning R-3327 rat prostatic cancers. This antitumor effect of linomide is host mediated. One possible mechanism involving the host is that linomide has antiangiogenic activity. An indication that linomide treatment has antiangiogenic activity is the observation that prostatic cancers from linomide treated rats have more focal necrosis than sized matched tumors from untreated rats. To directly test if linomide has antiangiogenic activity, a newly developed Matrigel based quantitative in vivo angiogenic assay was used. These experiments demonstrated that linomide has dose dependent, antiangiogenic activity in vivo in the rat Additional studies demonstrated that due to its antiangiogenic activity, linomide treatment of rats bearing prostate cancers resulted in a more than 40% decrease in tumor blood flow. Blood flow to a variety of non-tumor bearing organs was not decreased suggesting that linomide selectively inhibits angiogenesis and does not induce loss of established blood vessels. Using as a model the response of human umbilical vein endothelial cells to linomide treatment in a variety of in vitro assays, linomide was demonstrated to have cytostatic but not cytotoxic effect on human umbilical vein endothelial cells at a medium concentration of >100 pg/ml. In addition, both endothelial cell chemotactic migration and invasion are steps in angiogenesis inhibited by linomide treatment.

Original languageEnglish (US)
Pages (from-to)1833-1837
Number of pages5
JournalCancer Research
Volume53
Issue number8
StatePublished - Apr 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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