Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir

S. Liekens, J. Neyts, E. De Clercq, E. Verbeken, D. Ribatti, M. Presta

Research output: Contribution to journalArticle

Abstract

Cidofovir [(S)-HPMPC; (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] is an antiviral drug that has been approved for the treatment of cytomegalovirus retinitis in AIDS patients. Cidofovir also possesses potent inhibitory activity against various human papillomavirus-induced tumors in animal models and patients. In addition, cidofovir inhibits the development of murine polyomavirus-induced hemangiomas in rats by an as-yet-uncharacterized, antivirus-independent mechanism. Here we report the inhibitory effect of cidofovir on the development of virus-independent vascular tumors originated by basic fibroblast growth factor (FGF2)-overexpressing endothelial cells (FGF2-T-MAE cells). In vitro, cidofovir was cytostatic to FGF2-T-MAE cells at a 50% cytostatic concentration of 6.7 μg/ml. Cidofovir concentrations >25 μg/ml resulted in cytotoxicity because of induction of apoptosis. Cidofovir did not affect FGF2-T-MAE cell sprouting in three-dimensional fibrin gel and morphogenesis on Matrigel at noncytotoxic concentrations. In vivo, cidofovir (100 μg/egg) completely suppressed hemangioma formation on the chick chorioallantoic membrane (CAM) induced by intra-allantoic injection of FGF2-T-MAE cells, without affecting the formation of normal CAM vessels. Accordingly, cidofovir applied locally at 200 μg/disc, reduced neovascularization on the CAM by only 35%. Intratumoral or systemic administration of cidofovir caused a significant inhibition of the growth of s.c., J.p, or intracerebral FGF2-T-MAE xenografts in nude mice and severe combined immunodeficient mice. Drug-induced apoptosis was observed in FGF2-T-MAE tumors as soon as 2 days after the beginning of treatment. In conclusion, cidofovir appears to inhibit the growth of endothelium-derived tumors via induction of apoptosis without exerting a direct antiangiogenic activity.

Original languageEnglish
Pages (from-to)5057-5064
Number of pages8
JournalCancer Research
Volume61
Issue number13
Publication statusPublished - Jul 1 2001

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Organophosphonates
Fibroblast Growth Factor 2
Nucleosides
Blood Vessels
Neoplasms
Chorioallantoic Membrane
Cytostatic Agents
Hemangioma
Apoptosis
cidofovir
Cytomegalovirus Retinitis
Polyomavirus
SCID Mice
Growth
Fibrin
Morphogenesis
Heterografts
Nude Mice
Endothelium
Antiviral Agents

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Liekens, S., Neyts, J., De Clercq, E., Verbeken, E., Ribatti, D., & Presta, M. (2001). Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir. Cancer Research, 61(13), 5057-5064.

Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir. / Liekens, S.; Neyts, J.; De Clercq, E.; Verbeken, E.; Ribatti, D.; Presta, M.

In: Cancer Research, Vol. 61, No. 13, 01.07.2001, p. 5057-5064.

Research output: Contribution to journalArticle

Liekens, S, Neyts, J, De Clercq, E, Verbeken, E, Ribatti, D & Presta, M 2001, 'Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir', Cancer Research, vol. 61, no. 13, pp. 5057-5064.
Liekens S, Neyts J, De Clercq E, Verbeken E, Ribatti D, Presta M. Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir. Cancer Research. 2001 Jul 1;61(13):5057-5064.
Liekens, S. ; Neyts, J. ; De Clercq, E. ; Verbeken, E. ; Ribatti, D. ; Presta, M. / Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir. In: Cancer Research. 2001 ; Vol. 61, No. 13. pp. 5057-5064.
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