Abstract A2: Dauricine inhibits IGF-I-induced HIF-1α protein accumulation and VEGF expression

Abstract

Abstract A2 Dauricine (Dau), a bisbenzylisoquinoline alkaloid derivative isolated from the rhizome of Menispermum dauricum DC, has been found to have anticancer activities. However, the effect of Dau on tumor angiogenesis is still unclear. A growing body of evidence has demonstrated that hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) play an important role in tumor angiogenesis. In this study, we investigated the effect of Dau on HIF-1α and VEGF expression induced by insulin-like growth factor-I (IGF-I) in human breast cancer cells (MCF-7). Our results showed that Dau significantly inhibited IGF-I-induced HIF-1α protein accumulation, but had no effect on HIF-1α mRNA expression. Meanwhile, Dau also remarkably suppressed VEGF expression at both protein and mRNA levels in response to IGF-I. Mechanistically, we found that Dau suppressed IGF-I-induced HIF-1α and VEGF protein expression mainly via blocking the activation of PI-3K/AKT/mTOR signaling pathway. Functionally, we found that Dau dramatically abrogated IGF-I-stimulated formation of capillary tube-like structures in vitro. Taken together, our results suggested that Dau may be a promising antiangiogenic agent for human breast cancer. Supported by National Natural Science Foundation of China (No. 30872944) and Guangdong Administration of Traditional Chinese Medicine (No.2008166). Citation Information: Cancer Prev Res 2008;1(7 Suppl):A2.