Perillyl alcohol is an angiogenesis inhibitor

Heleni Loutrari, Maria Hatziapostolou, Vassoula Skouridou, Evangelia Papadimitriou, Charis Roussos, Fragiskos N. Kolisis, Andreas Papapetropoulos

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Aberrant angiogenesis is essential for the progression of solid tumors and hematological malignancies. Thus, antiangiogenic therapy is one of the most promising approaches to control cancer. In the present work, we examined the ability of perillyl alcohol (POH), a dietary monoterpene with well-established tumor chemopreventive and chemotherapeutic activity, to interfere with the process of angiogenesis. POH remarkably prevented new blood vessel growth in the in vivo chicken embryo chorioallantoic membrane assay and proved to be effective in inhibiting the morphogenic differentiation of cultured endothelial cells into capillary-like networks both in collagen gel and Matrigel models. In addition, POH reduced the cell number in a proliferation assay and induced apoptosis of endothelial cells as indicated by the POH-mediated increase of caspase-3 activity and DNA fragmentation. Consistent with the observed antisurvival effect, POH treatment resulted in a significant inhibition of Akt phosphorylation in endothelial cells. Finally, POH was able to differentially modulate the release of two important angiogenic regulators: vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2). POH decreased the release of VEGF from cancer cells but stimulated the expression of Ang2 by endothelial cells, indicating that it might suppress neovascularization and induce vessel regression. Overall, these data underscore the antiangiogenic potential of POH and suggest that POH, in addition to its anticancer activity, may be an effective agent in the treatment of angiogenesis-dependent diseases.

Original languageEnglish (US)
Pages (from-to)568-575
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume311
Issue number2
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Fingerprint

perilla alcohol
Angiogenesis Inhibitors
Endothelial Cells
Angiopoietin-2
Vascular Endothelial Growth Factor A
Neoplasms
Chorioallantoic Membrane
Monoterpenes
DNA Fragmentation
Hematologic Neoplasms

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Loutrari, H., Hatziapostolou, M., Skouridou, V., Papadimitriou, E., Roussos, C., Kolisis, F. N., & Papapetropoulos, A. (2004). Perillyl alcohol is an angiogenesis inhibitor. Journal of Pharmacology and Experimental Therapeutics, 311(2), 568-575. https://doi.org/10.1124/jpet.104.070516

Perillyl alcohol is an angiogenesis inhibitor. / Loutrari, Heleni; Hatziapostolou, Maria; Skouridou, Vassoula; Papadimitriou, Evangelia; Roussos, Charis; Kolisis, Fragiskos N.; Papapetropoulos, Andreas.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 311, No. 2, 01.11.2004, p. 568-575.

Research output: Contribution to journalArticle

Loutrari, H, Hatziapostolou, M, Skouridou, V, Papadimitriou, E, Roussos, C, Kolisis, FN & Papapetropoulos, A 2004, 'Perillyl alcohol is an angiogenesis inhibitor', Journal of Pharmacology and Experimental Therapeutics, vol. 311, no. 2, pp. 568-575. https://doi.org/10.1124/jpet.104.070516
Loutrari H, Hatziapostolou M, Skouridou V, Papadimitriou E, Roussos C, Kolisis FN et al. Perillyl alcohol is an angiogenesis inhibitor. Journal of Pharmacology and Experimental Therapeutics. 2004 Nov 1;311(2):568-575. https://doi.org/10.1124/jpet.104.070516
Loutrari, Heleni ; Hatziapostolou, Maria ; Skouridou, Vassoula ; Papadimitriou, Evangelia ; Roussos, Charis ; Kolisis, Fragiskos N. ; Papapetropoulos, Andreas. / Perillyl alcohol is an angiogenesis inhibitor. In: Journal of Pharmacology and Experimental Therapeutics. 2004 ; Vol. 311, No. 2. pp. 568-575.
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