Abstract #LB-283: The anti-angiogenic activity of sweet leaf tea extract is mediated by the down-regulation of bFGF and VEGF receptor (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Mounting evidence indicates that angiogenesis is essential for the proliferation and survival of number of malignant diseases, which suggests that inhibition of angiogenesis might be an effective therapeutic strategy. Anti-angiogenic therapies that target VEGF and VEGF receptor (VEGFR) are considered to be effective adjuncts to the treatment of solid tumors. Certain herbal extracts have long been considered effective in inhibition of angiogeneisis. Chinese sweet leaf tea, a hot water extract of Rubus suavissimus S. Lee (Rosaceae) (RUS) has been reported to have antiangiogenic activities evidenced by its ability to inhibit the angiogenic initiation and growth of human placental vein tissue (Liu et al., Phytother, Res. 20: 806-813, 2006) and experimental corneal neovascularization (Hakan, O.F., et al, Pharmaceu. Biol. 45: 44-47, 2007). Here we investigated the molecular mechanisms associated with the observed antiangiogenic effect of the RUS extract using HUVEC cells. Our preliminary data demonstrated that the RUS extract inhibited the proliferation of HUVEC cells (IC50 = 14.2 µg/ml) more strongly than that of cancer cells (IC50 ranging from 22.2 to 88.0 µg/ml) of A549, BRO, HT29, MDA-231, Panc-1 and PC3. The migration of HUVEC cells treated with the RUS extract (5 to 50 µg/ml) was markedly reduced compared to that of cells treated with the vehicle alone. This inhibitory effect was concentration dependent. The RUS extract showed partial inhibition of endothelial tubule formation at 50 µg/ml and complete inhibition at 100 µg/ml. When HUVEC cells were treated with the RUS extract (5 to 100 µg/ml), the expression of bFGF was markedly inhibited in a concentration dependent manner. In contrast, protein level of VEGF was slightly reduced and MMP2 remained unaffected by the treatment with RUS extract in HUVEC cells. To further confirm the involvement of VEGF pathway in sweet leaf tea induced anti-angiogenic activity, the protein level of tyrosine kinase receptor VEGFR2 (Flk-1/KDR), was examined. Intriguingly, the expression of Flk-1/KDR was significantly suppressed in HUVEC cells treated with the RUS extract regardless the presence or absence of VEGF. This inhibitory effect was concentration dependent. The 78% inhibition of bFGF by the RUS extract (100 \#956;g/ml) in HUVEC cells was further confirmed by the Panomics cytokine array analysis. Additionally, RUS extract at 100 µg/ml inhibited the expression of PDGF by 54%, G-CSF by 95%, and increased potent tumor angiogenesis inhibitor IP-10 (14-fold) in a concentration dependent manner. These results suggest that natural sweet leaf tea extract may have great potential to inhibit angiogenesis through down regulation of pro-angiogenic factor FGF and VEGF pathways. The active components responsible for anti-angiogenic effect of RUS extract are currently investigated and will be reported. This study was supported by NIH grant 1R21 AT002882-01A2 to Z. Liu.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-283.