N-acetylcysteine inhibits endothelial cell invasion and angiogenesis

Tania Cai, GianFranco Fassina, Monica Morini, Maria Grazia Aluigi, Luciana Masiello, Gabriella Fontanini, Francesco D'Agostini, Silvio De Flora, Douglas M. Noonan, Adriana Albini

Research output: Contribution to journalArticle

Abstract

The thiol N-acetylcysteine (NAC) is a chemopreventive agent that acts through a variety of mechanisms and can prevent in vivo carcinogenesis. We have previously shown that NAC inhibits invasion and metastasis of malignant cells as well as tumor take. Neovascularization is critical for tumor mass expansion and metastasis formation. We investigated whether a target of the anti-cancer activity of NAC could be the inhibition of the tumor angiogenesis-associated phenotype in vitro and in vivo using the potent angiogenic mixture of Kaposi's sarcoma cell products as a stimulus. Two endothelial (EAhy926 and human umbilical vein endothelial [HUVE]) cell lines were utilized in a panel of assays to test NAC ability in inhibiting chemotaxis, invasion, and gelatinolytic activity in vitro. NAC treatment of EAhy926 and HUVE cells in vitro dose-dependently reduced their ability to invade a reconstituted basement membrane, an indicator of endothelial cell activation. Invasion of HUVE cells was inhibited with an ID50 of 0.24 mM NAC, whereas inhibition of chemotaxis required a 10 fold higher doses, indicating that invasion is a preferential target. NAC inhibited the enzymatic activity and conversion to active forms of the gelatinase produced by endothelial cells. The matrigel in vivo assay was used for the evaluation of angiogenesis; NAC strongly inhibited neovascularization of the matrigel sponges in response to Kaposi's sarcoma cell products. NAC prevented angiogenesis while preserving endothelial cells, implying that it could be safely used as an anti-angiogenic treatment.

Original languageEnglish
Pages (from-to)1151-1159
Number of pages9
JournalLaboratory Investigation
Volume79
Issue number9
Publication statusPublished - Sep 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Cai, T., Fassina, G., Morini, M., Aluigi, M. G., Masiello, L., Fontanini, G., D'Agostini, F., De Flora, S., Noonan, D. M., & Albini, A. (1999). N-acetylcysteine inhibits endothelial cell invasion and angiogenesis. Laboratory Investigation, 79(9), 1151-1159.