Epigallocatechin-3-Gallate Inhibits IGF-I-Stimulated Lung Cancer Angiogenesis through Downregulation of HIF-l alpha and VEGF Expression

Background/Aims: Numerous studies have shown that epigallocatechin-3-gallate (EGCG), a polyphenol component extracted from green tea, can inhibit the growth and induce apoptosis of various types of human tumor cells. In this study, we evaluated the inhibitory effects of EGCG on the proangiogenic capabilities of A549 cells. Methods: A549 cells starved in serum-free culture medium for 24 h were pretreated with EGCG at various concentrations (0, 10, 25, 50, and 100 mu mol/l) for 1 h, followed by the addition of insulin-like growth factor-I (IGF-I) at the final concentration of 40 ng/ml and continued culturing for an additional 16 h. The in vitro angiogenesis analyzing test kit with ECMatrix (TM) gel was used to detect the formation of capillary tube-like structures. The mRNA expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) was determined by real-time PCR. The protein expression of HIF-1 alpha and VEGF was detected by Western blotting and ELISA, respectively. Results: EGCG significantly inhibited the formation of capillary tube-like structures on the surface of ECMatrix induced by IGF-I both in vitro and in vivo and reduced the level of hemoglobin in Matrigel plugs. In addition, EGCG was shown to significantly inhibit the IGF-I-induced upregulation of HIF-1 alpha protein expression. Meanwhile, EGCG at the concentration of 25 and 100 mu mol/l exhibited obvious inhibitory effects on IGF-I-induced VEGF expression (p < 0.01). Conclusion: Our results suggest that EGCG has potent inhibitory effects on tumor angiogenesis induced by IGF-I in human non-small cell lung cancer cells, which may possibly contribute to the down regulation of HIF-1 alpha and VEGF expression. (C) 2013 S. Karger AG, Basel