[Show abstract][Hide abstract] ABSTRACT: Angiogenesis is the result of intricate steps regulated by the balance between agonistic and antagonistic effectors. Disturbance of this balance leads to an 'angiogenic' switch critical for tumor development.
Using human umbilical vein endothelial cells (HUVEC) the effects of lupulone were analyzed on proliferation induced by angiogenic growth factors, transmembrane cell migration toward fibronectin and formation of a network of tubular-like structures on Matrigel.
Lupulone (2.5-50 microg/ml) induced a concentration-dependent inhibition of HUVEC proliferation and chemotaxis. Lupulone caused a significant reduction of closed capillary-like structures in Matrigel indicating a strong inhibitory effect on neovascularisation. In mice receiving lupulone (20 mg/kg/day) in drinking water for 21 days, new vessel formation was reduced by 50% in matrigel plugs implanted under the skin when compared with controls.
The present data demonstrate that lupulone is able to inhibit angiogenesis in vitro and in vivo. Lupulone emerges as a potential chemopreventive agent when considering its strong antiangiogenic properties.
Preview · Article · Jan 2008 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: Potassium-sparing diuretics have different effects on angiogenesis that may mediate some abilities to treat cardiovascular diseases. The aim of the current study was to compare the effects of spironolactone and an active metabolite, canrenone, or a derivative, eplerenone, and amiloride, a diuretic without affecting mineralocorticoid activity, on the proliferation of human umbilical vein endothelial cells (HUVEC) and on angiogenesis in fibrin gel chambers implanted in rats.
We measured the effects of spironolactone, canrenone, eplerenone, and amiloride on the proliferation of HUVEC in the presence or absence of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We also examined the effects of these compounds on migration and capillary tube formation by HUVEC. Finally, the effects of the compounds on neovessel formation in vivo were investigated by implanting Wistar rats for 14 days with perforated Plexiglas chambers containing rat fibrin.
Spironolactone and amiloride inhibited the proliferation of HUVEC, but canrenone and eplerenone had no effect. The inhibitory effect of spironolactone was not prevented by VEGF or bFGF. Aldosterone had no effect on spironolactone-induced inhibition of HUVEC proliferation. Spironolactone induced a dose-dependent reduction of both cell chemotaxis and capillary tube formation. In fibrin gel chambers, spironolactone and amiloride significantly reduced the numbers of both peripheral and central neovessels. Canrenone and eplerenone, in contrast, had no antiangiogenic effect.
Spironolactone and amiloride significantly inhibited angiogenesis in vitro and in the fibrin gel chamber in vivo. Spironolactone antiangiogenic effects are unrelated to antimineralocorticoid activity.
No preview · Article · Dec 2006 · Journal of Hypertension
[Show abstract][Hide abstract] ABSTRACT: High linear energy transfer (LET) radiation have the ability to kill cancer cells resistant to conventional radiotherapy. On the other hand, protocols combining radiotherapy and chemotherapy are effective in eradicating certain inoperable cancers. In this study, we investigated the cytotoxicity of a co-treatment with fast neutrons and cisplatin in a human glioblastoma cell line, U-87. Cells cultured in vitro were irradiated with p(65)+Be neutrons in the presence of cisplatin. Cell survival and the induction of apoptosis and premature senescence were assessed at different time intervals thereafter, using a variety of methods. A marked reinforcement of the cytotoxicity was obtained when irradiation and cisplatin were associated. This reflected both an amplification of the apoptotic process and the induction of premature cell senescence. The efficiency of a combination between fast neutrons and cisplatin in inducing cell death in U-87 is more than additive. The present data concur with those we previously reported in a mouse lymphoma and suggest the potential utility of platinum compounds as adjuncts to future cancer therapy protocols using high-LET radiation.