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 language | English |
|---|---|
| Pages (from-to) | 5057-5064 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 61 |
| Issue number | 13 |
| Publication status | Published - Jul 1 2001 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Inhibition of fibroblast growth factor-2-induced vascular tumor formation by the acyclic nucleoside phosphonate cidofovir
AU - Liekens, S.
AU - Neyts, J.
AU - De Clercq, E.
AU - Verbeken, E.
AU - Ribatti, D.
AU - Presta, M.
PY - 2001/7/1
Y1 - 2001/7/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 11431341
AN - SCOPUS:0035394723
VL - 61
SP - 5057
EP - 5064
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 13
ER -