Significant Antiangiogenic Activity Research Articles

Anti-Angiogenic and Anti-Proliferative Activity of 4-2-(5-bromo-1H-indol-2-carbonyl)-N-(4-methoxyphenyl) Hydrazine-1-carbothioamide: Ex-vivo and in vitro Study.

Angiogenesis, the formation of new blood vessels, stimulates tumor growth and spread by delivering oxygen and nutrients, and is a key component of metastasis. This work aimed to evaluate the anti-angiogenic properties of a new synthesized compound. Rat aorta angiogenesis assay was used to evaluate the ability of the carbothioamide derivative to inhibit blood vessels sprouting. The tetrazolium (MTT) assay was used to evaluate the anti-proliferative effect of the synthetic compound on human umbilical vein endothelial cell line (HUVECs) and A549 lung cancer cells line. The (2, 2-diphenyl-1-picrylhydrazyl) DPPH was used to investigate the free radical scavenging action. The study showed that the compound has anti-angiogenic activity with IC50 56.9 µg/mL, moreover the compound managed to inhibit the proliferation of HUVECs and A549 cells (IC50 76.3 µg/mL and 45.5 µg/mL, respectively), and The IC50 concentration for free radical scavenging activity of the compound was 27.8 µg/ml. The study concluded that the compound has significant anti-angiogenic activity may be related to its significant anti-proliferative effect against HUVECs, these pharmacological effect may attributed to its potent free radical scavenging activity.

Analysis of the Anticancer Mechanism of OR3 Pigment from Streptomyces coelicolor JUACT03 Against the Human Hepatoma Cell Line Using a Proteomic Approach.

This study assessed OR3 pigment, derived from Streptomyces coelicolor JUACT03, for its anticancer potential on HepG2 liver cancer cells and its safety on HEK293 normal cells. OR3 induced apoptosis and inhibited HepG2 cell proliferation, confirmed by caspase activation, Sub-G1 phase cell cycle arrest, and reduced colony formation. Proteomic analysis revealed altered expression of proteins associated with ribosomal function, mRNA processing, nuclear transport, proteasome activity, carbohydrate metabolism, chaperone function, histone regulation, and vesicle-mediated transport. Downregulation of proteins in MAPKAP kinase1, EIF2, mTOR, and EIF4 pathways contributed to apoptosis and cell cycle arrest. Changes in c-MYC, FUBP1 target proteins and upregulation of Prohibitin-1 (PHB1) were also noted. Western blot analysis supported alterations in eIF2, mTOR, and RAN pathways, including downregulation of RAB 5, c-MYC, p38, MAPK1, and MAPK3. OR3 exhibited significant anti-angiogenic activity in the in ovo CAM assay. In summary, OR3 demonstrated strong anticancer effects, inducing apoptosis, hindering proliferation, and displaying antiangiogenic properties. These findings highlight OR3's potential as an anticancer drug candidate, warranting further in vivo exploration.

Dually Active Apigenin-Loaded Nanostructured Lipid Carriers for Cancer Treatment.

Cancer is one of the major causes of death worldwide affecting more than 19 million people. Traditional cancer therapies have many adverse effects and often result in unsatisfactory outcomes. Natural flavones, such as apigenin (APG), have demonstrated excellent antitumoral properties. However, they have a low aqueous solubility. To overcome this drawback, APG can be encapsulated in nanostructured lipid carriers (NLC). Therefore, we developed dual NLC encapsulating APG (APG-NLC) with a lipid matrix containing rosehip oil, which is known for its anti-inflammatory and antioxidant properties. Optimisation, physicochemical characterisation, biopharmaceutical behaviour, and therapeutic efficacy of this novel nanostructured system were assessed. APG-NLC were optimized obtaining an average particle size below 200 nm, a surface charge of -20 mV, and an encapsulation efficiency over 99%. The APG-NLC released APG in a sustained manner, and the results showed that the formulation was stable for more than 10 months. In vitro studies showed that APG-NLC possess significant antiangiogenic activity in ovo and selective antiproliferative activity in several cancer cell lines without exhibiting toxicity in healthy cells. APG-NLC containing rosehip oil were optimised. They exhibit suitable physicochemical parameters, storage stability for more than 10 months, and prolonged APG release. Moreover, APG-NLC were internalised inside tumour cells, showing the capacity to cause cytotoxicity in cancer cells without damaging healthy cells.

Antiangiogenic activity and the isolation of five phenolic compounds from Euphorbia milii ethyl acetate solvent extract

Background: Euphorbia milii a medicinal plant from Euphorbia genus, has been used traditionally as a cure for cancer, warts and as a hepatoprotective agent in tropical areas like China, Myanmar, Brazil, and Pakistan. Previous literature investigated the effect of E. milii flower extract in some types of cancer cell lines. Objective: This study aims to evaluate the antiangiogenic activity of the ethyl acetate fraction of the methanolic crude extract of E. milii, in addition to the detection and isolation of some phenolic compounds. Materials and Methods: Detection of the phenolic compounds was achieved using TLC and HPLC chromatographic methods. Isolation was achieved by preparative layer chromatography based on Rf values. The isolated compounds were identified through HPLC and TLC, in addition to FTIR. The anti-angiogenic activity was evaluated employing rat aorta ring anti-angiogenesis assay. Results: Five phenolic compounds were isolated in this study namely, Luteolin, Apigenin, Isorhamnetin, Coumaric acid and Quercitrin. However phenolic compounds detected via TLC were, Silybin, Luteolin, Apigenin, Isorhamnetin, Coumaric acid and Quercitrin. Interestingly, HPLC detected Coumarin, Rutin, Catechin and Quercetin. Anti-angiogenesis assay found that E. milii ethyl acetate fraction inhibited new blood vessel growth significantly (p<0.05) by 94 + 3.6% as compared with DMSO negative control (0%), while when compared with Suramin positive control (100%) it showed no significant difference (p>0.05). Conclusion: E. milii showed significant anti angiogenic activity of its ethyl acetate fraction, suggesting the association of E. milii traditional use as anticancer and phenolic content, current data must be further evaluated.

LEGUME INDIAN BEAN (PHASEOLUS VULGARIS) PARTIALLY PURIFIED ANTI-NUTRITIONAL PROTEIN FACTOR EXHIBIT ANTI-OXIDANT, IMMUNOMODULATORY AND ANTI-CANCER PROPERTIES

Objective: This study was aimed to access one of the hidden ANF in Indian bean and assessment of its antioxidant, immunomodulatory, antiangiogenic, and anti-cancer properties. Methods: Indian beans were processed and evaluated for the presence of ANF through HA activity. Bean-ANF was partially purified by ammonium sulfate precipitation (ASP) and dialysis. Obtained Partially Purified bean-ANF (PPb-ANF) resolved on 12% SDS-PAGE, analyzed protease digestibility. The immunogenicity of PPb-ANF was characterized by producing polyclonal antibodies and checked for the presence of natural antibodies in healthy human sera. Pharmacological studies of PPb-ANF were assessed through anti-oxidant, immunogenic, anti-angiogenic and anti-cancer assays. Results: Partially purified Bean-ANF (PPb-ANF) showed significant specific HA activity up to 150 Units/mg compared to crude extract 9.3 of Units/mg. The PPb-ANF was identified to have more than 90% homogeneity in purity with an observed M W of 30-32 kDa. PPb-ANF showed significant pepsin digestive stability up to 2 h at 37 ᵒC and appears digestive resistant. Rabbit produced anti-PPb-ANF IgG polyclonal antibody on immunization and exhibited immunogenic properties. Natural human IgG and IgE antibodies were found in the non-atopic human sera against PPb-ANF, indicative of its immunogenicity. Pharmacological studies of PPb-ANF confirmed its potent antioxidant activity. At 400 µg of PPb-ANF showed the highest around 90% DPPH activity and at 150 µg of PPb-ANF showed 89% inhibitory lipid peroxidation activity. The PPb-ANF showed 70% (3 μg) and 40% (1.5 μg) inhibitory in blood vessel density compared to control and exhibited significant anti-angiogenic activity. The PPb-ANF showed a significant (*p<0.05.) reduction in solid tumor weight upon dose-2 treatment (50 mg/kg body weight) and also increased lifespan up to 70 d compared with the control tumor model. Conclusion: PPb-ANF was identified as digestive-resistant, hemagglutinin with a molecular weight of 30-32 kDa. The protein is immunogenic and has potential antioxidant, antiangiogenic and anti-cancer properties. Further purification and mechanistic-based pharmacological characterization might explore this protein as a potential anti-cancer molecule.

Antiproliferative Activity of Buddleja saligna (Willd.) against Melanoma and In Vivo Modulation of Angiogenesis.

Melanoma cells secrete pro-angiogenic factors, which stimulates growth, proliferation and metastasis, and therefore are key therapeutic targets. Buddleja saligna (BS), and an isolated triterpenoid mixture (DT-BS-01) showed a fifty percent inhibitory concentration (IC50) of 33.80 ± 1.02 and 5.45 ± 0.19 µg/mL, respectively, against melanoma cells (UCT-MEL-1) with selectivity index (SI) values of 1.64 and 5.06 compared to keratinocytes (HaCat). Cyclooxygenase-2 (COX-2) inhibition was observed with IC50 values of 35.06 ± 2.96 (BS) and 26.40 ± 4.19 µg/mL (DT-BS-01). BS (30 µg/mL) significantly inhibited interleukin (IL)-6 (83.26 ± 17.60%) and IL-8 (100 ± 0.2%) production, whereas DT-BS-01 (5 µg/mL) showed 51.07 ± 2.83 (IL-6) and 0 ± 6.7% (IL-8) inhibition. Significant vascular endothelial growth factor (VEGF) inhibition, by 15.84 ± 4.54 and 12.21 ± 3.48%, respectively, was observed. In the ex ovo chick embryo yolk sac membrane assay (YSM), BS (15 µg/egg) significantly reduced new blood vessel formation, with 53.34 ± 11.64% newly formed vessels. Silver and palladium BS nanoparticles displayed noteworthy SI values. This is the first report on the significant anti-angiogenic activity of BS and DT-BS-01 and should be considered for preclinical trials as there are currently no US Food and Drug Administration (FDA) approved drugs to inhibit angiogenesis in melanoma.

Antiangiogenic activity of hydroalcoholic flowers extract of Lantana Camara

In current research, Lanata camara, flower hydroalcoholic extract; was evaluated for anti-angiogenic properties. The anti-angiogenic potency was evaluate by chick chorioallantoic membrane (CCAM) (in ovo), endothelial cell proliferation (ECP), transwell migration (TMA) and Matrigel cord-like morphogenesis (MCLM) assay (in vitro) along with sponge implantation method(SIM) (in vivo). The results compared to standard anti-angiogenic drug bevacizumab (BEV) and also with the angiogenic factor vascular endothelial growth factor at 500 nM concentration. In CCAM test results, the quantity of branching points(BPS) and angiogenic score(ANS) were found significant at 10-5 M and 10-4 M. Significant reductions in mass of sponge, quantity of blood vessels produced, and hemoglobin content(HB)wasfound at various concentrations of Lanata camara flower hydroalcoholic extract in SIM method. The results of human umbilical vein endothelial cells (HUVEC) the test samples (1-100 nM) displayed major inhibition of proliferation and migration and a decline in network length of cord-like tubes (CLT) in a dosage-dependent pattern. Lanata Camara, flower hydroalcoholic extract has significant anti-angiogenic activity by inhibition of cell proliferation, migration, and CLTdevelopment, that results from blocking of the cell proliferation on endothelial cells.

Anti-angiogenic, apoptotic and matrix metalloproteinase inhibitory activity of Withania somnifera (ashwagandha) on lung adenocarcinoma cells

IntroductionWithania somnifera belongs to the family Solanaceae, known as Queen of medicinal plants for its enormous use in the medicinal field. Traditionally ashwagandha is used to treat several neurological disorders. This study evaluates the cytotoxic, apoptotic, antiangiogenic and matrix metalloproteinase (MMP) inhibitory activity of W. somnifera on lung adenocarcinoma. MethodologyAqueous and ethanolic extracts were prepared from the roots of the W. somnifera. Qualitative and quantitative phytochemical analyses were performed using the standard protocols. Cytotoxicity was assessed using MTT assay. Further experiments were carried out with IC50 concentration of the extract. Apoptosis and DNA damage were evaluated using AO-EB dual staining, Hoechst staining and Comet assay. Effect of the extract on cell migration was evaluated using scratch assay. Angiogenesis inhibition was evaluated using in ovo CAM assay and angiogenic pathway alterations were evaluated using qRT-PCR and western blotting. Autophagy induction was studied via western blotting. ResultsIn this study, we found antioxidant activity and the presence of certain secondary metabolites in the ethanolic extracts. The extract showed cytotoxic activity on lung adenocarcinoma cells with an IC50 of 99.7 μg/ml. The extract showed significant anti-angiogenic, apoptotic and autophagy induction activity. W. somnifera extract induced significant decrease in the cell migration at lower concentrations indicating the anti-migratory potential. ConclusionOur investigation revealed ethanolic extract of W. somnifera possess significant anti-angiogenic and MMP inhibitory activity and helps in inhibiting the lung adenocarcinoma cells proliferation. Further, our study revealed that the enhanced autophagy induction and apoptotic effects of W. somnifera are responsible for the potential anticancer activity of the extract.

Evaluation of antiangiogenic and antiproliferative potential of ethanolic extracts of Andrographis echioides using in vitro and in ovo assays.

Andrographis echioides is a prevalently used medicinal herb in South Asian countries. Scientific researches with the extracts of A. echioides revealed its antipyretic, anti-inflammatory, antimicrobial, ulceroprotective, and hepatoprotective properties. This study was done to elucidate antiproliferative and antiangiogenic potential of ethanolic extracts of A. echioides (EEAE) by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and chorioallantoic membrane (CAM) assay. EEAE was prepared using Soxhlet apparatus with ethanol after being sun-dried and powdered. MCF 7 (human invasive breast ductal carcinoma) cell lines retaining attributes of differentiated mammary epithelium with both estrogen and progesterone receptors were treated with EEAE, and antiproliferative effect was seen using Mosmann method of MTT assay using 5-fluorouracil (5-FU) as a comparator. The evaluation of antiangiogenic potential of EEAE was done by comparing mean vessel density (MVD) in chick CAM after treatment with EEAE, thalidomide, and vascular endothelial growth factor (VEGF) using CAM assay, an in ovo assay. EEAE displayed antiproliferative activity from low to high concentrations with MTT assay. The IC50 of EEAE and 5-FU was 62.5 and 15.6 μg/ml, respectively (P < 0.05). The exhibition of its antiangiogenic activity increased proportionately with increasing concentration. VEGF increased MVD by 45.94%; thalidomide decreased it by 53.76%. There was a decrease of MVD by 5.91%, 20.46%, and 35.95% at concentrations of 25, 50, and 100 μg of EEAE, respectively. EEAE possessed significant antiangiogenic and antiproliferative activity, making them a promising substrate in the development of a novel anticancer drug and can be successfully used in the therapy of various cancers after establishment of the anticancer effects in animal models and subsequently in clinical trials.

Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models

Gemcitabine (Gem), a nucleoside analog, is a preferred choice of treatment for pancreatic cancer (PCa) and often used in combination therapy against wide range of solid tumors. It is known to be rapidly inactivated in blood by cytidine deaminase. The objective of the study was to improve the systemic stability and anticancer activity of modified Gem termed 4-N-stearoylGem (4NSG) In this study, the IC50 values of 4NSG treated MiaPaCa-2 and primary pancreatic cancer (PPCL-46) cultures were significantly lower when compared with gemcitabine hydrochloride (GemHCl) treated cultures. In acute toxicity study, liver enzyme level of aspartate aminotransferase (AST) of the control mice was not significantly different from AST levels of 4NSG and GemHCl treated mice. However, alanine aminotransferase (ALT) level of control mice (67 ± 5 mUnits/mL) was significantly lower compared with ALT levels of GemHCl (232 ± 28 mUnits/mL) and that of 4NSG (172 ± 22 mUnits/mL) (p < 0.0001). More importantly, ALT level of 4NSG was lower than ALT level of GemHCl (p < 0.05). Although ALT levels were elevated, pathological images of liver and kidney tissues of control, GemHCl and 4NSG treated mice revealed no architectural changes and no significant change in mice weight was observed during treatment. The bioavailability (AUC) of 4NSG was 3-fold high and significantly inhibited the tumor growth as compared with equivalent dose of GemHCl. Immunohistochemical staining revealed that 4NSG significantly inhibited the expression vascular endothelial growth factor (VEGF) receptor. The study is unique because it established, for the first time, enhanced anticancer activity of 4NSG against pancreatic patient-derived xenograft (PDX) mouse model and PPCL-46 cells compared with Gem. 4SGN enhanced pharmacokinetic profile and improved the therapeutic efficacy of the standard-of-care Gem. Lastly, 4GSN showed a remarkable tumor growth inhibition and revealed significant antiangiogenic activity in 4GSN treated pancreatic PDX tumor.

Selenium Nanoparticles Synthesized Using Pseudomonas stutzeri (MH191156) Show Antiproliferative and Anti-angiogenic Activity Against Cervical Cancer Cells.

PurposeSelenium nanoparticles (SeNP) have several applications in the field of biotechnology, including their use as anti-cancer drugs. The purpose of the present study is to analyze the efficacy of green synthesis on the preparation of SeNP and its effect on their anti-cancer properties.MethodsA bacterial strain isolated from a freshwater source was shown to efficiently synthesize SeNP with potential therapeutic properties. The quality and stability of the NP were studied by scanning electron microscopy, X-ray diffraction, zeta-potential and FTIR analysis. A cost-effective medium formulation from biowaste having 6% banana peel extract enriched with 0.25 mM tryptophan was used to synthesize the NP. The NP after optimization was used to analyze their anti-tumor and anti-angiogenic activity. For this purpose, first, the cytotoxicity of the NP against cancer cells was analyzed by MTT assay and then chorioallantoic membrane assay was performed to assess anti-angiogenic activity. Further, cell migration assay and clonogenic inhibition assay were performed to test the anti-tumor properties of SeNP. To assess the cytotoxicity of SeNP on healthy RBC, hemolysis assay was performed.ResultsThe strain identified as Pseudomonas stutzeri (MH191156) produced phenazine carboxylic acid, which aids the conversion of Se oxyanions to reduced NP state, resulting in particles in the size range of 75 nm to 200 nm with improved stability and quality of SeNP, as observed by zeta (ξ) potential of the particles which was found to be −46.2 mV. Cytotoxicity of the SeNP was observed even at low concentrations such as 5 µg/mL against cervical cancer cell line, ie, HeLa cells. Further, neovascularization was inhibited by upto 30 % in CAMs of eggs coinoculated with SeNp when compared with untreated controls, indicating significant anti-angiogenic activity of SeNP. The NP also inhibited the invasiveness of HeLa cells as observed by decreased cell migration and clonogenic proliferation. These observations indicate significant anti-tumor and anti-angiogenic activity of the SeNP in cervical cancer cells.ConclusionP. stutzeri (MH191156) is an efficient source of Se NP production with potential anti-angiogenic and anti-tumor properties, particularly against cervical cancer cells.

A sulfated polysaccharide from the edible flesh of Cipangopaludina chinensis inhibits angiogenesis to enhance atherosclerotic plaque stability

Sulfated polysaccharide (CCPSs) of Cipangopaludina chinensis has shown significant antiangiogenic activity. In view of the closely relationship between angiogenesis and atherosclerotic plaque vulnerability, we speculated that CCPSs may stabilize atherosclerotic plaques by inhibiting angiogenesis. The purpose of this study was to demonstrate a correlation between the role of CCPSs in stabilizing plaques and its inhibition of angiogenesis, and further clarify its regulatory mechanism. The results suggested that CCPSs can enhance the stable components and inhibit the vulnerability factors to reduce vulnerability index of atherosclerotic plaques, thus making it more stable. Its mechanism was proved to be closely related with anti-angiogenesis in plaques. This inhibitory effect of CCPSs on angiogenesis in plaques was also found to be achieved by regulating the PI3K/Akt/mTOR signaling pathway. The results indicated that CCPSs is a promising candidate for treatment of atherosclerotic unstable plaques.

Antiangiogenic activity of zinc and zinc-sorafenib combination using the chick chorioallantoic membrane assay: A descriptive study.

Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Furthermore, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated. A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 μg/embryo with sorafenib 1 and 2 μg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels. Zinc 2.5 μg/embryo showed significant (P < 0.05) antiangiogenic activity, as compared to the control group. However, its effect was not comparable to that of sorafenib 2 μg/embryo. The combination of zinc 2.5 μg/embryo with sorafenib 2 μg/embryo did not show an additive/synergistic effect. The combination of zinc 2.5 μg/embryo with sorafenib 1 μg/embryo produced an antiangiogenic activity which was comparable (P > 0.05) to that of sorafenib 2 μg/embryo. Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor.

Parietin as an efficient and promising anti-angiogenic and apoptotic small-molecule from Xanthoria parietina

Lichens that are exclusive symbiotic organisms composed of fungus and alga, are considered as a wealthy source of biologically and pharmacologically active small-molecules thanks to the tight metabolic relationship between symbiotic partners. We herein report cytotoxic, anti-angiogenic and apoptotic profile of a lichen derived small-molecule named parietin. Parietin was isolated from the acetone extract of Xanthoria parietina (L.) Th.Fr (1860), Teloschistaceae, which was gathered from Afyon, Turkey. AlamarBlue™ cell viability, lactate dehydrogenase membrane leakage and PicoGreen™ dsDNA quantitation assays were used to determine the cytotoxic concentrations of parietin on cisplatin-resistant BRCA2-mutated human breast TNM stage IV adenocarcinoma (HCC1428), human breast ductal carcinoma (T-47D), and human umbilical vein endothelial (HUVEC) cells. Additionally, cell adhesion, endothelial tube formation, reactive oxygen species accumulation and active caspase 3 determination assays were employed to identify the anti-angiogenic and apoptotic efficiency of parietin. Low concentrations of parietin such as 50 and 100 µM showed a significant anti-angiogenic and apoptotic activity though the half-maximal inhibitory concentration (IC50) values were higher than 600 µM on the cells. On the other hand, it was observed that parietin shows less cytotoxic and membrane degradative activities on healthy HUVEC cells than the HCC1428 and T-47D breast cancer cells. Parietin seems to be a promising anti-angiogenic and apoptotic lichen metabolite for the further investigations.

Clavukoellians A-F, Highly Rearranged Nardosinane Sesquiterpenoids with Antiangiogenic Activity from Clavularia koellikeri.

Six new nardosinane-type sesquiterpenoids, clavukoellians A-F (1-6), together with one new neolemnane-type sesquiterpene, 4- O-deacetylparalemnolin D (7), were isolated from the marine soft coral Clavularia koellikeri. The structures of compounds 1-7 were elucidated by NMR spectroscopy, ECD analysis, and quantum chemical calculation methods. Compounds 1 and 7 demonstrated significant antiangiogenic activities in wound healing assays on HUVECs.

Antiangiogenic Iridoids from Stachys ocymastrum and Premna resinosa.

In this paper, the isolation of one new iridoid glucoside, 6β-acetoxyipolamiide (1: ), and thirteen (2: - 14: ) known congeners from two Lamiaceae species, Stachys ocymastrum and Premna resinosa, leaf extracts is reported. The structural determination of the isolated compounds was performed by mono- and bidimensional NMR spectroscopic analysis as well as MS experiments. The isolates were assayed for their antiangiogenic activity by two in vivo models, zebrafish embryos and chick chorioallantoic membrane assays. The compounds with a significant antiangiogenic activity in both assays were β-hydroxyipolamiide (2: ), ipolamiide (3: ), and buddlejoside A5 (8: ). 6-O-α-l-(3″-O-p-Methoxycinnamoyl-4″-O-acetyl)rhamnopyranosyl catalpol (13: ) and 6-O-α-l-(2″-trans-caffeoyl)rhamnopyranosyl catalpol (6: ) showed the best antiangiogenic response on blood vessel growth in zebrafish embryos, whereas saccatoside (10: ) and 6-O-α-l-(2″-O - : p-methoxycinnamoyl-3″-O-acetyl)rhamnopyranosyl catalpol (14: ) resulted in a strong reduction of capillary formation in the chorioallantoic membrane assay.

Antiangiogenic potential of Jatropha curcas latex in the chick chorioallantoic membrane model

AIMS: To perform a physicochemical and phytochemical characterization of Jatropha curcas latex and to investigate its antiangiogenic potential. METHODS: We performed an initial physicochemical characterization of J. curcas latex using thermal gravimetric analyses and Fourier Transform Infrared spectroscopy. After that, phenols, tannins and flavonoids were quantified. Finally, the potential of J. curcas latex to inhibit angiogenesis was evaluated using the chick chorioallantoic membrane model. Five groups of 20 fertilized chicken eggs each had the chorioallantoic membrane exposed to the following solutions: (1) water, negative control; (2) dexamethasone, angiogenesis inhibitor; (3) Regederm®, positive control; (4) 25% J. curcas latex diluted in water; (5) 50% J. curcas latex diluted in water; and (6) J. curcas crude latex. Analysis of the newly-formed vascular net was made through captured images and quantification of the number of pixels. Histological analyses were performed to evaluate the inflammation, neovascularization, and hyperemia parameters. The results were statically analyzed with a significance level set at p ˂0.05.RESULTS: Physicochemical characterization showed that J. curcas latex presented a low amount of cis-1.4-polyisoprene, which reduced its elasticity and thermal stability. Phytochemical analyses of J. curcas latex identified a substantial amount of phenols, tannins, and flavonoids (51.9%, 11.8%, and 0.07% respectively). Using a chick chorioallantoic membrane assay, we demonstrated the antiangiogenic potential of J. curcas latex. The latex induced a decrease in the vascularization of the membranes when compared with neutral and positive controls (water and Regederm®). However, when compared with the negative control (dexamethasone), higher J. curcas latex concentrations showed no significant differences.CONCLUSIONS: J. curcas latex showed low thermal stability, and consisted of phenols, tannins, and flavonoids, but little or no rubber. Moreover, this latex demonstrated a significant antiangiogenic activity on a chick chorioallantoic membrane model. The combination of antimutagenic, cytotoxic, antioxidant and antiangiogenic properties makes J. curcas latex a potential target for the development of new drugs.

Anionic and Cationic Vitamin E-TPGS Mixed Polymeric Phospholipid Micellar Vehicles.

Berberine (Brb) is an active isoquinoline alkaloid occurring in various common plant species, with well-known potential for cancer therapy. Earlier reports has shown that Brb not only augments the efficacy of antineoplastic chemotherapy and radiotherapy, but it also exhibits direct anti-mitotic, and pro-apoptotic activities, plus significant anti-angiogenic and anti-metastatic activities in a variety of solid tumors. Notwithstanding its low systemic toxicity, a few pharmaceutical limitations severely hamper the application of Brb in cancer therapy (namely, very slight aqueous solubility and exceedingly low membrane permeability; combined with poor systemic pharmacokinetic, PK, profile).Lipid-based nanocarriers, amphiphilic mixed micelles (Mic) composed of polymeric phospholipid conjugates and PEG-succinate ester of tocopherol were investigated as promising strategy, to improve Brb delivery into tumors. Following physicochemical characterization of micellar Brb, in vitro release studies in simulated physiological media were performed, combined with PK-simulation and in vitro assays of cytotoxicity and direct apoptosis induction in different human prostate cancer cell lines (PC3 and LNPaC).Optimized stealth PEG-PE/TPGS-mixed micelles achieved efficient solubilization of Brb to potentially improve its systemic PK profiles (>30-fold). Our mixed micellar platform resulted in significant enhancement of the pro-apoptotic action and overall anticancer efficacy of Brb, against various in vitro (monolayer and spheroid) models of prostate cancers.

Assessment of Antioxidant and Antiangiogenic Activities of Ethanolic Root extract of Cassia occidentalis

Context: The process by which new blood vessels grow is termed as Angiogenesis. In the adult, except for a few physiological processes such as menses, wound healing, and placental formation, all angiogenic processes are pathologic. Angiogenic imbalance in which proangiogenic factors predominate over antiangiogenic factors is tumor angiogenesis. Inhibition of blood vessel growth, is a way to prevent tumour growth and other angiogenesis-dependent diseases is antiangiogenesis. Aim: The present study aims to determine the antioxidant and antiangiogenic activities of ethanolic root extract of Cassia occidentalis. Materials and methods: Antioxidant activity was evaluated against various free radicals like Nitric oxide scavenging, Hydroxyl radicals and Phosphomolybdenum assay using Ascorbic acid as standard. The most common study used to evaluate the antiangiogenic activity is chick embryo chorioallantoic membrane (CAM) , an in vivo assay. Results: Ethanolic root extract of Cassia occidentalis exhibited a significant antioxidant status which is evident from their IC50 values 21.42 ug/mL in Nitric oxide scavenging method, 22.3 ug/mL in hydroxyl radical. In phosphomolybdenum assay, there is concentration-dependent increase in absorbance. The results obtained are similar to that of standard drug ascorbic acid. In anti-oxidant activity, percentage inhibition was determined by calculating IC50 values . By decreasing the capillary networks proliferation in a dose (50 to 150 µg/egg) dependent manner which is probably related to the inhibition of neovascularization. The present study results indicated significant antiangiogenic effect on chorioallantoic membrane. Conclusion: The plant extract has shown good free radical scavenging activity indicative from their percentage inhibition. It also exhibits significant antiangiogenic activity, and this is a possible rationale for its folkloric use as an anticancer agent.

Design and Synthesis of Novel Thioethers Derived from 1,5-Diphenyl-6- thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones as Antiangiogenic Agents

Background: In attempts to discover new antiangiogenic entities, a novel series of thioethers derived from 6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidine-4(5H)ones was considered and designed. &lt;/P&gt;&lt;P&gt; Methods: Virtual screening was carried out through docking of the compounds into the vascular endothelial growth factor and matrix metalloproteinase-9 binding sites. Molecular docking studies were performed using Lamarckian Genetic Algorithm. Compounds possessing lowest ligandprotein pairwise interaction energies were synthesized and screened for their antiproliferative activities against five cancer cell lines namely MHCC97H (liver), MDA-MB 231 (Breast), Colo205 (Colon), A549 (lung), A498 (kidney) and IC50 values were determined for the most potent compounds. Additionally, they were tested for their antiangiogenic activities by testing their ability to inhibit Human Umbilical Vein Endothelial Cell (HUVEC), cord formation and migration in response to chemoattractant. Results: Three compounds 2a, 2b and 5b showed significant antiangiogenic activities. The allyl thioether 2b was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Additionally, 2a, 2b and 5b, contrary to TNP-470, interfered with the migration of HUVECs in response to vascular endothelial growth factor rather than endothelial cells proliferation or cord formation. Compounds 2a, 2b and 5b were also investigated for their inhibitory effects on MMPs to investigate the relationship between their angiogenic activity and MMPs. Results revealed that compound 2b was the most effective MMP-9 inhibitor in this series. Additionally, compound 2b reduced the expression levels of VEGF and pERK1/2. Conclusion: Our results suggest that compound 2b is considered as a promising antiangiogenic agent by targeting VEGF and MMP-9.