• Title, Summary, Keyword: anti-angiogenic

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Production and Characterization of an Anti-Angiogenic Agent front Saccharomyces cerevisiae K-7

  • Jeong, Seung-Chan;Lee, Dae-Hyoung;Lee, Jong-Soo
    • Journal of Microbiology and Biotechnology
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    • v.16 no.12
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    • pp.1904-1911
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    • 2006
  • The cell-free extracts of 250 yeasts were screened for their in vitro anti-angiogenic activity, to develop a new cancer metastasis inhibitor. Saccharomyces cerevisiae K-7 was selected as the producer of the anti-angiogenic agent, because it had the highest anti-angiogenic activity. The anti-angiogenic agent was produced maximally from hydrolysates of Saccharomyces cerevisiae K-7, when the yeast was cultured in yeast extract-peptone-dextrose medium at 30$^{\circ}C$ for 24 h, and cell-free extracts were than digested with pepsin for 4 h at 37$^{\circ}C$. The anti-angiogenic agent was further purified by ultrafiltration, Sephadex G-25 gel permeation chromatography and reverse-phase HPLC, and the anti-angiogenic activity of the final purified preparation was 72.7% at 10 $\mu$M/egg. The purified anti-angiogenic agent was found to originate from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) molecule of Saccharomyces cerevisiae K-7, and its peptide sequence was Val-Ser-Trp-Tyr-Asp-Asn-Glu-Tyr-Gly-Tyr-Ser-Thr-Arg-Val-Val-Asp. In the MTT assay, the shape of the HT-l 080 cell was clearly changed to a circular type at 0.2 mM purified anti-angiogenic agent. This result indicated that the growth of the HT-I080 cell was significantly inhibited at 0.2 mM of the purified anti-angiogenic agent. The MMP activity of the treated HT-l080 cells was not affected, evidenced by the gelatin zymography, indicating that the anti-angiogenic mechanism of the purified anti-angiogenic agent is not mediated through MMP activity.

Screening of Anti-angiogenic Activity from Plant Extracts (식물 추출물의 혈관신생 억제 효능 검색)

  • Kim, Joon-Sik;Park, Byoung-Young;Park, Eun-Kyu;Lee, Hee-Suk;Hahm, Jong-Cheon;Bae, Ki-Hwan;Kim, Min-Young
    • Korean Journal of Pharmacognosy
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    • v.37 no.4
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    • pp.253-257
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    • 2006
  • We examined anti-angiogenic effects of water extracts from 32 plant materials (20 Korean medicinal plants and 12 western herbs) using cell-based anti-angiogenic assay, HUVEC tube formation assay, and then we found that 7 plant extracts inhibited HUVEC tube formation strongly. The plant materials which showed anti-angiogenic effects are Cinnamomi Ramulus, Atractylodis Rhizoma alba, Polygalae Radix, Myristicae Semen, Artemisiae Iwayomogii Herba, leaves of Rosmarinus officinalis, and leaves of Melissa officinalis. We also investigated inhibitory effects of these anti-angiogenic herbal extracts on MMP (matrix metalloproteinase) activity which has important roles in angiogenesis. Among extracts tested in this study, water extract of Melissa officinalis showed the most potent anti-angiogenic and MMP inhibitory activity.

Anti-angiogenic, Anti-inflammatory and Anti-nociceptive Activities of Vanillin in ICR Mice

  • Lim, Eun-Ju;Kang, Hyun-Jung;Jung, Hyun-Joo;Song, Yun-Seon;Lim, Chang-Jin;Park, Eun-Hee
    • Biomolecules & Therapeutics
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    • v.16 no.2
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    • pp.132-136
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    • 2008
  • The current study aimed to assess some novel pharmacological activities of vanillin. Vanillin inhibited the chick chorioallantoic membrane (CAM) angiogenesis. Vanillin had anti-inflammatory activity using the acetic acid-induced permeability model in mice. Anti-nociceptive activity of vanillin was shown using the acetic acid-induced writhing test in mice. Vanillin inhibited production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) but not cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Vanillin decreased the level of iNOS mRNA in the LPS-activated macrophages. Taken together, these results suggest that vanillin can have anti-angiogenic, anti-inflammatory and anti-nociceptive activities in ICR Mice.

VEGF-VEGFR Signals in Health and Disease

  • Shibuya, Masabumi
    • Biomolecules & Therapeutics
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    • v.22 no.1
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    • pp.1-9
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    • 2014
  • Vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) system has been shown to play central roles not only in physiological angiogenesis, but also in pathological angiogenesis in diseases such as cancer. Based on these findings, a variety of anti-angiogenic drugs, including anti-VEGF antibodies and VEGFR/multi-receptor kinase inhibitors have been developed and approved for the clinical use. While the clinical efficacy of these drugs has been clearly demonstrated in cancer patients, they have not been shown to be effective in curing cancer, suggesting that further improvement in their design is necessary. Abnormal expression of an endogenous VEGF-inhibitor sFlt-1 has been shown to be involved in a variety of diseases, such as preeclampsia and aged macular degeneration. In addition, various factors modulating angiogenic processes have been recently isolated. Given this complexity then, extensive studies on the interrelationship between VEGF signals and other angiogenesis-regulatory systems will be important for developing future strategies to suppress diseases with an angiogenic component.

Anti-Angiogenic Activity of Acalycixenolide E, a Novel Marine Natural Product from Acallycigorgia inermis

  • Kwon, Ho-Jeong;Kim, Jin-Hee;Jung, Hye-Jin;Kwon, Yong-Guen;Kim, Min-Young;Rho, Jung-Rae;Shin, Jong-Heon
    • Journal of Microbiology and Biotechnology
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    • v.11 no.4
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    • pp.656-662
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    • 2001
  • Angiogenesis is known as a crucial process in the growth and spreading of tumor cells. Accordingly, the effective inhibition of this process would appear to be a promising way to cure angiogenesis-related diseases, including cancer. This study demonstrates that acalycixenolide E (AX-E) from the marine organism Acalycigorgia inermis exhibits a potent anti-angiogenic activity both in vitro and in vivo. AX-E inhibits the bFGF-induced proliferation of HUVECs in a dose dependent manner, along with the bFGF-induced migration, invasion, and tube formation of HUVECs. Moreover, AX-E potently inhibits the in vivo neovascularization of the chorioallantoic membranes (CAMs) of growing chick embryos. interestingly, AX-E suppresses the expression of metalloproteases 2 and 9, yet shows no effect on their activities. The novel chemical structure and potent anti-angiogenic activity of AX-E will be of great value in elucidating the molecular mechanism of angiogenesis as well as in the development of a novel anti-angiogenic drug.

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4-[(N-Imidazol-2-ylmethyl)anilino]pyranopyridine Analogs as Novel Anti-Angiogenic Agents

  • Lee, Sun-Kyung;Chae, Sun-Mi;Yi, Kyu-Yang;Kim, Nak-Jeong;Oh, Chang-Ho
    • Bulletin of the Korean Chemical Society
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    • v.26 no.4
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    • pp.619-628
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    • 2005
  • We attempted to replace a benzopyran ring of 4-[(N-imidazol-2-ylmethyl)-4-chloroanilino]benzopyran, previously discovered as anti-angiogenic agent with antitumor activity, with pyranopyridines. The [3,2-c]-, [3,2-b]-, [2,3-c]-, and [2,3-b]-pyranopyridines with -(imidazol-2-ylmethyl)aniline moiety at the 4-position, were synthesized respectively, and evaluated for primary anti-angiogenic properties through primary cultured HUVEC tube formation assay. From this study, we found that the pyranopyridine ring, especially [3,2-b]- and [2,3-c]-isomer, can replace the benzopyran ring of the compound 1 and can be optimized through the introduction of substituents both on the pyranopyridine ring and the aniline moiety for the identification of a novel anti-angiogenic agent.

Anti-Inflammatory, Antioxidant, Anti-Angiogenic and Skin Whitening Activities of Phryma leptostachya var. asiatica Hara Extract

  • Jung, Hyun-Joo;Cho, Young-Wook;Lim, Hye-Won;Choi, Hojin;Ji, Dam-Jung;Lim, Chang-Jin
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.72-78
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    • 2013
  • This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine.

[18F]FET PET is a useful tool for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic glioblastoma mouse model

  • Kim, Ok-Sun;Park, Jang Woo;Lee, Eun Sang;Yoo, Ran Ji;Kim, Won-Il;Lee, Kyo Chul;Shim, Jae Hoon;Chung, Hye Kyung
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.248-256
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    • 2018
  • O-2-$^{18}F$-fluoroethyl-l-tyrosine ($[^{18}F]FET$) has been widely used for glioblastomas (GBM) in clinical practice, although evaluation of its applicability in non-clinical research is still lacking. The objective of this study was to examine the value of $[^{18}F]FET$ for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic mouse model of GBM. Human U87MG cells were implanted into nude mice and then bevacizumab, a representative anti-angiogenic drug, was administered. We monitored the effect of anti-angiogenic agents using multiple imaging modalities, including bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT). Among these imaging methods analyzed, only $[^{18}F]FET$ uptake showed a statistically significant decrease in the treatment group compared to the control group (P=0.02 and P=0.03 at 5 and 20 mg/kg, respectively). This indicates that $[^{18}F]FET$ PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, $[^{18}F]FET$ uptake was confirmed to be a significant parameter for predicting the prognosis of anti-angiogenic drug (P=0.041 and P=0.007, on Days 7 and 12, respectively, on Pearson's correlation; P=0.048 and P=0.030, on Days 7 and 12, respectively, on Cox regression analysis). However, results of BLI or MRI were not significantly associated with survival time. In conclusion, this study suggests that $[^{18}F]FET$ PET imaging is a pertinent imaging modality for sensitive monitoring and accurate prediction of treatment response to anti-angiogenic agents in an orthotopic model of GBM.

Anti-cell Proliferative and Anti-angiogenic Potential of Andrographolide During 7,12-Dimethylbenz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis

  • Singh, Arjun Kumar;Manoharan, Shanmugam;Vasudevan, Krishnamurthy;Rajasekaran, Duraisamy;Manimaran, Asokan;Suresh, Kathiresan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6001-6005
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    • 2013
  • Our aim was to explore anti-cell proliferative and anti-angiogenic potential of andrographolide by analyzing the expression pattern of cell proliferative (PCNA, Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral tumors which were histopathologically diagnosed as well differentiated squamous cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the histological abnormalities but also down regulated the expression of PCNA, VEGF and Cyclin D1. The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential.

Anti-Angiogenic Activities of Gliotoxin and 1ts Methylthio-Derivative, Fungal Metabolites

  • Lee, Hee-Jung;Lee, Jeong-Hyung;Hwang, Bang-Yeon;Kim, Hang-Sub;Lee, Jung-Joon
    • Archives of Pharmacal Research
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    • v.24 no.5
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    • pp.397-401
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    • 2001
  • In the search for new naturally occurring angiogenic inhibitory we found that culture broths from two unidentified fungal strains exerted potent inhibitory activities on capillary-like tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Two active compounds were isolated by bioassay-guided separation and their structures were identified as gliotoxin (1) and its derivative methylthiogliotoxin (2) by spectroscopic analyses. These compounds significantly inhibited the migration of HUVEC assessed by in vitro wounding migration assay and exhibited at least 10 times more potent inhibition of proliferation of HUVECs as compared with that of cancer cell lines such as HeLa, MCF-7, and KB 3-1 cells. Especially, gliotoxin having disulfide group exerted more potent activities than methylthiogliotoxin, suggesting that gliotoxin could be a useful compound for further study as an anti-angiogenic agent.

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