Canstatin protein, a newly found angiogenesis inhibitor, has powerful anti-angiogenesis effect. Canstatin is the N terminal fragment of collagen IV alpha2 chain NC1 domain. Its distinct anti-cancer effect in mouse model and low toxicity has not only made it a promising new anti-cancer drug candidate, but also drawn much attention of researchers. The detection, denomination, biological characters and mechanism of canstatin protein, and also the prospect of its application were summarized.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Antineoplastic Agents ; pharmacology ; Collagen Type IV ; pharmacology ; Humans ; Mice

Angiogenesis Inhibitors ; pharmacology ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Neovascularization, Pathologic ; drug therapy ; Phytotherapy

OBJECTIVETo study the inhibition effect of celastrol on neovascularization.

METHODSThe effect of celastrol on the in vitro proliferation of endothelial cell of vessel (ECV) was examined by MTT assay. The effect of celastrol on endothelial cell migration, tube formation on Matrigel and Chick chorioallantoic membrane angiogenesis was also examined. Matrigel plug assay was used to evaluate the effect of celastrol on angiogenesis in vivo.

RESULTSThe proliferation of ECV was inhibited significantly by celastrol with IC(50) being 1.33 microg/ml. Celastrol inhibited endothelial cell migration and tube formation in a dose-dependent manner. Celastrol also inhibited angiogenesis both in Matrigel plug of mouse model and in chick chorioallantoic membranes.

CONCLUSIONCelastrol, which can inhibit angiogenesis, could be developed as an antiangiogenic drug.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Endothelial Cells ; drug effects ; Mice ; Mice, Inbred BALB C ; Triterpenes ; pharmacology

OBJECTIVETo investigate the effects of two histone deacetylase (HDAC) inhibitors, valproic acid (VPA) and TSA, on the expression of vascular endothelial growth factor (VEGF) and its receptor KDR of the leukemia cell line Kasumi-1 cells, and to explore their potential mechanism in leukemia angiogenesis.

METHODKasumi-1 cells were treated with VPA and TSA at different concentrations for 3 days. The mRNA and protein expression levels of VEGF and KDR were determined by semi-quantitative RT-PCR and Western blot, and the bFGF mRNA by semi-quantitative RT-PCR.

RESULTSAs compared with that of control groups, VPA at 3 mmol/L downregulated the VEGF mRNA expression level for VEGF(121) from 0.632 ± 0.014 to 0.034 ± 0.004 and for VEGF(165) from 0.526 ± 0.021 to 0.015 ± 0.001, for KDR mRNA from 0.258 ± 0.034 to 0.038 ± 0.000, and for bFGF mRNA from 0.228 ± 0.017 to 0.086 ± 0.015. TSA downregulated the VEGF mRNA and KDR mRNA at concentration of 100 nmol/L, but its effect on bFGF mRNA only at higher concentration.

CONCLUSIONHDAC inhibitors might inhibit the leukemia angiogenesis by regulating the expression of VEGF and its recptor.

Angiogenesis Inducing Agents ; Cell Line ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; RNA, Messenger ; genetics ; Valproic Acid ; pharmacology ; Vascular Endothelial Growth Factor A

AIM: To investigate the chemical constituents and their biological activities of the aerial parts of Euphorbia tibetica. METHOD: Compounds were isolated and purified by various chromatographic methods, and their structures were elucidated through the use of extensive spectroscopic techniques including 2D-NMR, the structures of compounds 5 and 6 were confirmed by single-crystal X-ray crystallography. Bioactivities of all the isolated compounds were evaluated by the MTT method on A549 and anti-angiogenesis assay. RESULTS: One new compound, methyl 4-epi-shikimate-3-O-gallate (1), together with twenty-three known constituents (2-24) were isolated from the aerial parts of E. tibetica. CONCLUSION Compound 1 is new, and the other compounds were isolated from this plant for the first time. Compounds 5-7, 9, 11, 17, 18 and 20 exhibited inhibitory effects on the growth of human lung cancer cell A549 and compounds 5, 7, 12, 13, 17 and 19 showed anti-angiogenic effects in a zebrafish model.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Cell Line ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Euphorbia ; chemistry ; Growth Inhibitors ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Zebrafish

Alkaloids ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; Ginsenosides ; pharmacology ; Humans ; Lymphatic Metastasis ; prevention & control ; Pyrazines ; pharmacology ; Quinolizines

OBJECTIVEProstate cancer (PCa) is a major health concern. Calliandra portoricensis (CP) is traditionally known for its analgesic, anti-ulcerogenic and anticonvulsant properties. However, its antiproliferative properties for PCa still need to be investigated.

METHODSAntioxidant activities of CP were determined by 1,1-diphenyl-2-picryhydrazyl (DPPH) and hydroxyl (OH(-)) radicals-scavenging methods. PC-3 and LNCaP (androgen-refractory and androgen-dependent PCa-derived cell lines) were cultured and treated with CP (10, 50 and 100 μg/mL). Effects of CP on cells were determined by cytotoxicity assay (lactate dehydrogenase, LDH) and viability assay (sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate, XTT). DNA fragmentation was detected by cell death detection enzyme-linked immunosorbent assay plus kit. CP was tested as an inhibitor of angiogenesis using chicken chorioallantoic membrane (CAM) assay.

RESULTSCP showed significant scavenging of DPPH and OH(-) radicals. CP significantly (P<0.05) inhibited lipid peroxidation in a dose-dependent manner. Precisely, CP (10, 50 and 100 μg/mL) inhibited PC-3 and LNCaP growth by 7%, 74% and 92%, and 27%, 73%, and 85% respectively at 48 h. CP had low toxicity in vitro at its half inhibitory concentration dose. Detection of cell death induced by CP at 50 μg/mL showed higher enrichment factors in LNCaP (7.38±0.95) than PC-3 (3.48±0.55). Also, treatment with CP (50 μg/mL) significantly reduced network of vessels in CAM, suggesting its antiangiogenic potential.

CONCLUSIONCalliandra portoricensis elicited antioxidant, antiangiogenic and antiproliferative effects in PCa cells.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antioxidants ; pharmacology ; Fabaceae ; Humans ; Male ; Plant Extracts ; pharmacology ; Plant Roots ; Prostatic Neoplasms ; drug therapy ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of angiogenesis inhibitor and its combine with chemical drug in suppressing the growth of adenoid cystic carcinoma (ACC).

METHODSAcc-M cells were inoculated subcutaneous into BABL/C nu/nu mice. The mice were divided into control, different dose of TNP-470 treatment groups, 5-Fu treatment group and TNP-470 plus 5-Fu treatment group. Treatments were given 48 hours after inoculation. The mice were sacrificed on the 22nd day and excised tumors were weighted. Tumors were also investigated by immunohistochemistry and ultrastructural observations.

RESULTSTNP-470 100 mg/kg/qod efficiently inhibited the growth of Acc-M tumors. TNP-470 30 mg/kg/qod combined with 50 mg/kg/week 5-Fu also resulted in significant growth inhibit of the tumors. TNP-470 suppressed tumor growth by inhibiting neovascularization, therefore inducing apoptosis of Acc-M cells. All experimental groups had different degrees of VEGF and bFGF express.

CONCLUSIONSince ACC is a slow developing tumor, blood supply is not so sufficient as sarcomas. Angiogensis inhibitor may inhibit its growth in high dosage. Combining medium dosage of angiogensis inhibitor with chemical drug may have synergistic result in inhibiting ACC growth.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; Carcinoma, Adenoid Cystic ; drug therapy ; Cell Line, Tumor ; Cyclohexanes ; pharmacology ; Fluorouracil ; pharmacology ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; pharmacology

The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor Ⅱ(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1β, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1β, and IL-6.
Angiogenesis Inhibitors/pharmacology* ; China ; Human Umbilical Vein Endothelial Cells ; Humans ; Neovascularization, Pathologic/drug therapy* ; Vascular Endothelial Growth Factor A/metabolism*

Zebrafish has become an important model organism in many fields of biomedical studies and been increasingly used in Chinese materia medica studies in recent years. This article summarized the achievements and prospect for zebrafish as a pharmacological and toxicological tool in the study and development of Chinese materia medica.
Angiogenesis Inducing Agents ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Animals ; Disease Models, Animal ; Materia Medica ; pharmacology ; therapeutic use ; toxicity ; Medicine, Chinese Traditional ; Memory Disorders ; prevention & control ; Neovascularization, Physiologic ; drug effects ; Zebrafish