Anti-angiogenic effect of furanodiene on HUVECs in vitro and on zebrafish in vivo.

Furanodiene is an active ingredient of the traditional Chinese medicine, Rhizoma Curcumae, commonly used for the treatment of cancer in China. To investigate the anti-cancer property of Rhizoma Curcumae, this study describes the anti-angiogenic activities of furanodiene in human umbilical vein endothelial cells (HUVECs) in vitro and in zebrafish in vivo. HUVECs were treated with different doses of furanodiene in the presence or absence of vascular endothelial growth factor (VEGF). The anti-proliferative effect of furanodiene was measured using the XTT assay. The anti-migration and anti-invasion activities of this compound were investigated with a wound-healing migration model and a three-dimensional cell invasion model, respectively. The effects of furanodiene on HUVEC differentiation were assessed by in vitro tube formation in Matrigel™. The expression of related proteins was detected by Western blot. Morphological observations of zebrafish were evaluated in transgenic Tg (fli1: EGFP) zebrafish embryos. Our results showed that furanodiene exposure could significantly inhibit the proliferation of HUVECs in a dose-dependent manner and inhibit VEGF-induced proliferation at a low dose. Relative to the VEGF-induced control, the number of invading and migrating cells was significantly reduced in the furanodiene-treated groups. Furanodiene also dramatically suppressed tube formation and p-Akt (Ser473), p-Erk 1/2 (Thr202/Tyr204), ICAM-1, p-p85 (Ser428) as well as p85 protein expression. Furthermore, exposure to furanodiene inhibited angiogenesis in the zebrafish model. This study demonstrated that furanodiene exposure exhibits a potential anti-angiogenic effect through suppression of endothelial cell growth, invasion, migration and tube formation via regulation of the PI3K pathway. This potential anti-angiogenic effect of furanodiene may play an important role in the anti-tumor activity of the traditional Chinese medicine, Rhizoma Curcumae.

Zhong ZF ，Hoi PM ，Wu GS ，Xu ZT ，Tan W ，Chen XP ，Cui L ，Wu T ，Wang YT ... -  《-》

Anti-tumor and anti-angiogenic effects of Macrothelypteris viridifrons and its constituents by HPLC-DAD/MS analysis.

Macrothelypteris viridifrons is widely distributed in south of China and has been used as folk medicine to treat cancer, hydropsy, and traumatic bleeding. To investigate the chemical constituents and the anti-tumor and anti-angiogenic effects of Macrothelypteris viridifrons. An HPLC-DAD/MS technique was used to determine the flavonoid profile of Macrothelypteris viridifrons. The anti-tumor effect of Macrothelypteris viridifrons was evaluated by in vivo mice bearing H22 hepatoma cells transplantation tumor model. And the anti-angiogenic activity was investigated by measuring the effects on the in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the in vivo zebrafish model was applied to evaluate the anti-angiogenic effect of Macrothelypteris viridifrons. 18 flavonoids were identified from Macrothelypteris viridifrons. Administration of Macrothelypteris viridifrons significantly inhibited the tumor growth and the expression of vascular endothelial growth factor (VEGF) and CD34. Meanwhile, Macrothelypteris viridifrons showed significant inhibition on proliferation, migration and tube formation of HUVECs in vitro and the intersegmental vessels formation in zebrafish model. Macrothelypteris viridifrons showed significant anti-tumor and anti-angiogenic effects and might be developed as a novel anti-tumor drug.

Wei A ，Zhou D ，Ruan J ，Cai Y ，Xiong C ，Wu G ... -  《-》

Ruboxistaurin, a PKCbeta inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt.

Nakamura S ，Chikaraishi Y ，Tsuruma K ，Shimazawa M ，Hara H ... -  《-》

Angiogenic efficacy of simplified 2-herb formula (NF3) in zebrafish embryos in vivo and rat aortic ring in vitro.

Diabetic foot ulceration results in high risk of lower extremity amputation, and represents a significant health care expenditure worldwide. Radix Astragali (RA) and Radix Rehmanniae (RR) are widely used Chinese medicinal herbs in treating diabetes, and have shown positive effects in enhancing wound healing in diabetic foot ulcer animal model. The angiogenic efficacy of NF3, a simplified 2-herb formula consisting of RA and RR in 2:1 ratio, was investigated. Median lethal concentration (LC50) and median effective concentration (EC50) were determined by treating zebrafish embryos with different concentrations of NF3 from 20 hpf to 72 hpf. The angiogenic activity of NF3 was examined in zebrafish embryos in vivo and by rat aortic ring assay in vitro. Cell cycle analysis of endothelial cells induced by NF3 was analyzed by flow cytometry using transgenic zebrafish Tg(fli1:EGFP). Real-time PCR was used to analyze mRNA expression profiles of selected genes involved in VEGF, FGF and MAPK pathways. NF3 enhanced blood vessel formation as indicated by extra growth of intersegmental vessels in zebrafish embryos, and increased microvessels formation in rat aortic ring. NF3 also enhanced endothelial cells proliferation as shown by increased percentage of cells accumulating in S phase and G2/M phase of the cell cycle. NF3 exposure significantly induced up-regulation of VEGF-A, Flk-1, fgf1 and bRaf expression in zebrafish embryos. Our results demonstrated that NF3 was effective in promoting angiogenesis in zebrafish embryos and by rat aortic ring assay, which provided scientific basis to support the use of NF3 as potential therapeutics in treating diabetic foot ulceration.

Tse HY ，Hui MN ，Li L ，Lee SM ，Leung AY ，Cheng SH ... -  《-》

Rhizoma Paridis ethanol extract selectively inhibits the proliferation of HUVECs comparing to Lovo cells and shows anti-angiogenesis effects in a mouse model.

Rhizoma Paridis, a traditional Chinese Medicine, was identified to be cytotoxic to cancer cells. The present study was designed to investigate the potential anti-angiogenic and antitumor effect of the ethanol extract of Rhizoma Paridis (RPE) in vitro and in vivo. The cytotoxic effect of RPE against human colon cancer Lovo cells and human umbilical vein endothelial cells (HUVECs) was examined using MTT assay. We also tested the effect of RPE on tube formation, migration, apoptosis and cell cycle of HUVECs. Moreover, Lovo subcutaneous xenograft was applied to study the antitumor and anti-angiogenesis effect of RPE in vivo. RPE exerted a higher inhibition effect on the proliferation of HUVECs than Lovo cells. The tube formation and cell migration were also significantly inhibited in the presence of RPE in a concentration-dependent manner though the significant inhibition effects were observed at the cytotoxic dose. RPE induced cell apoptosis and G0-G1 cell cycle arrest of HUVECs. In vivo, significant tumor growth inhibition was observed in human colon cancer xenografts established by Lovo cells, accompanying by a marked decrease in MVD. Our current study exhibited that RPE has a selective cytotoxity against HUVECs comparing to Lovo cells and also demonstrated significant anti-angiogenic effect in vivo.

Qian X ，Zhu L ，Hu J ，Li M ，Xie L ，Wang L ，Yu L ，Liu B ... -  《-》