• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8435-8440
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• 2014

Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.108.2-108.2
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• 2003

Kaempferol, a flavonol compound, has been reported as the anti-oxidant and anti-angiogenic agent and it has been found to inhibit cell growth in vitro. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in development of atherosclerosis. In this study, we examined the anti-proliferative effect and its mechanism on rat aortic VSMCs treated by kaempferol. kaempferol significantly inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic VSMCs in concentration-dependent manner by cell count and ［$^3$H］-thymidine incorporation assay. (omitted)

• Archives of Pharmacal Research
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• 제20권6호
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• pp.539-544
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• 1997

Anti-metastatic activities of IH901, an intestinal bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo. Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT 1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

• Toxicological Research
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• 제33권4호
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• pp.273-282
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• 2017

Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

• Biomolecules & Therapeutics
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• 제14권1호
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• pp.30-35
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• 2006

Tissue-type plasminogen activator (t-PA) is a multidomain serine protease containing two kringle domains, TK1-2. Previously, Pichia-derived recombinant human TK1-2 has been reported as an angiogenesis inhibitor although t-PA plays an important role in endothelial and tumor cell invasion. In this work, in order to improve in vivo efficacy of TK1-2 through elimination of immune reactivity, we mutated wild type TK1-2 into non-glycosylated form (NE-TK1-2) and examined whether it retains anti-angiogenic activity. The plasmid expressing NE-TK1-2 was constructed by replacing $Asn^{l17}\;and\;Asn^{184}$ with glutamic acid residues. After expression in Pichia pastoris, the secreted protein was purified from the culture broth using S-sepharose and UNO S1-FPLC column. The mass spectrum of NE-TK1-2 showed closely neighboring two peaks, 19631.87 and 19,835.44 Da, and it migrated as one band in SDS-PAGE. The patterns of CD-spectra of these two proteins were almost identical. Functionally, purified NE-TK1-2 was shown to inhibit endothelial cell migration in response to bFGF stimulation at the almost same level as wild type TK1-2. Therefore, the results suggest that non-glycosylated NETK1-2 can be developed as an effective anti-angiogenic and anti-tumor agent devoid of immune reactivity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권2호
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• pp.147-154
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• 2002

Genistein that is a component of soy has been reported to have a protective effect on the carcinogenesis of various tumors and to inhibit the growth of a wide variety of tumor cell in vitro. Angiogenesis is an essential process for the carcinogenesis, growth, invasion and metastasis of cancer and genistein has been suggested to act as natural anti-angiogenic agent. The purpose of this study was to evaluate the effects of genistein on the vascular endothelial growth factor (VEGF) expression in hamster buccal pouch oral carcinogenesis model induced by 9, 10-dimethyl 1,2-benzanthracene (DMBA). Experimental group that were supplied with 0.1mg/day genistein were sacrificed by time schedules and routinely processed for immunohistochemical examination of VEGF. In genistein treated group, carcinogenesis was retarded with respect to the acanthosis, hyperkeratosis, and epithelial dysplasia. Immunohistochemical study showed that the VEGF protein of genistein group was less expressed than that of the control group. (p<0.05) Thus, it is postulated that genistein has chemopreventive effect on the oral carcinogenesis, and this chemopreventive effect, at least partly, is originated from the anti-angiogenic effect of genistein

• 한국약용작물학회지
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• 제15권5호
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• pp.311-314
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• 2007

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important angiogenic molecules associated with tumor-induced neovascularization. This study was carried out to investigate inhibitory effect of extracts from root of Rehmannia glutinosa LIBOSCHITZ (Rehmannia Radix and Rehmannia Radix Preparata) on endothelial cell proliferation. The methanol extracts from the medicinal herb were fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. Among the four fractions, the n-butanol fraction from R. Radix on exhibited highly effective inhibition (${\approx}79%$ inhibition) on the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and then ethyl acetate fraction from R. Radix (${\approx}45%$ inhibition) at the concentration of $100\;{\mu}g/ml$. The n-butanol fraction efficiently blocked the VEGF- and bFGF-induced HUVEC proliferation in a dose-dependent manner, but did not affect the growth of HT1080 human fibrosarcoma cells. The n-butanol fraction more efficiently blocked the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and VEGF- and bFGF-induced human umbilical vein endothelial cell proliferation than the fraction from R. Radix Preparata. Our results suggest that Rehmannia Radix may be used as a candidate for developing anti-angiogenic agent.

• Natural Product Sciences
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• 제13권2호
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• pp.128-131
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• 2007

Tumor angiogenesis is a critical step f3r the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. This study was carried out to investigate inhibitory effect of extracts from root cortex of Paeonia suffruticosa Andrews on VEGF binding to VEGF receptor. The MeOH extract from P. suffrutiocosa Andr. inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ more than 45% at the concentration of 100 ${\mu}$g/mL. The MeOH extract was further fractionated into n-hexane, ethyl acetate, n-BuOH, and aqueous fractions. Among the four fractions, the ethyl acetate fraction from the root cortex of P. suffruticosa Andr. exhibited highly effective inhibition (${\approx}$ 79% inhibition) and then n-BuOH fraction (${\approx}$ 45% inhibition) on the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ at the concentration of 100 ${\mu}$g/mL. The ethyl acetate fraction from the root cortex of P. suffruticosa Andr. more efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation, than the growth of HT1080 human fibrosarcoma. Our results suggest that P. suffruticosa Andr. may be used as a candidate fur developing anti-angiogenic agent.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.93-100
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• 2014

Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like $H_2DCFDA$, JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.

• Fisheries and Aquatic Sciences
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• 제17권3호
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• pp.305-311
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• 2014

Dieckol is a polyphenol compound isolated from brown algae that has anti-oxidant, anti-inflammatory, and anti-tumor activity. We examined the anti-angiogenic effects of dieckol in endothelial cells under hypoxic conditions. Treatment with $CoCl_2$, a hypoxic mimetic agent, increased proliferation, adhesion, migration, and tube formation in HUVECs, as well as vessel sprouting in rat aortic rings, which correlated well with increased expression of hypoxia-inducible factor 1-alpha ($HIF1{\alpha}$) and ${\beta}1$-integrin. Dieckol suppressed $CoCl_2$-induced adhesion, migration, and tube formation in HUVECs and vessel sprouting in rat aortic rings. Dieckol treatment decreased $CoCl_2$-induced overexpression of $HIF1{\alpha}$ and its downstream signaling molecules, including ${\beta}1$-integrin/Fak, Akt/eNOS, and p38 MAPK. These results suggest that dieckol is a novel angiogenesis inhibitor and a potential treatment for angiogenesis-dependent diseases in humans, such as malignant tumors.