Abstract
A78
Angiogenesis, the formation of new blood vessels from the preexisting network, is now recognized to be a necessary process for tumor growth and dissemination. We have observed that the anti-tumor effect after treatment with chemopreventive agents is often due to their anti-angiogenic activity, a concept that we coined as ‘angioprevention’. We previously observed that various molecules are able to act within the tumor micro-environment inhibiting the recruitment and/or the activation of endothelial cells and phagocytes of the innate immunity. >Here we examined the angiopreventive action of the retinoic acid derivative Rexinoid LG100268. Rexinoids selectively bind the nuclear receptor transcription factors known as retinoid X receptors and modulate the activity of entire regulatory networks. In particular we investigated the activity of Rexinoid LG100268 both in vitro and in vivo. In the in vitro matrigel morphogenesis assay 500nM LG100268 succeed in preventing HUVECs from forming capillary-like structures. However, LG100268 did not affect cell growth or show toxicity or apoptosis induction in HUVECs in vitro. In vivo in the matrigel sponge assay 20nM LG100268 mixed with matrigel turns out to reduce vessel formation. Systemic administration of 1uM LG100268 by i.p. injection also significantly inhibited angiogenesis in vivo. >The data suggest that LG100268 is a promising agent for chemoprevention and therapy of cancer.
Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA