• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.2081-2086
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• 2015

Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of $20{\mu}L/mL$. AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of $11.5{\pm}0.5{\mu}L/mL$ and $12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$) or M-AG (${\geq}12\mu}L/mL$) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of ${\geq}0.4{\mu}L/mL$. This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component.

• Journal of Microbiology and Biotechnology
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• 제17권8호
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• pp.1338-1343
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• 2007

Angiogenesis is an essential step in tumor progress and metastasis. Accordingly, small molecules that inhibit angiogenesis would appear to be a promising way to cure angiogenesis-related diseases, including cancer. In the present study, we report that streptochlorin, a small molecule from marine actinomycete, exhibits a potent antiangiogenic activity. The compound potently inhibited endothelial cell invasion and tube formation stimulated with vascular endothelial cell growth factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to the cells. In addition, streptochlorin inhibited TNF-${\alpha}$-induced $NF-{\kappa}B$ activation in the newly developed cell-based reporter gene assay. These data demonstrate that streptochlorin is a new inhibitor of $NF-{\kappa}B$ activation and can be a basis for the development of novel anti-angiogenic agents.

• Journal of Microbiology and Biotechnology
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• 제12권5호
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• pp.829-833
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• 2002

Angiogenesis is an essential event in a variety of physiological and pathological processes. Therefore, effective inhibition of this event is a promising strategy for treating angiogenesis-related diseases, including cancer. The current study investigated two unique bafilomycin-type macrolide inhibitors of angiogenesls, PC-766B' (1) and PC-766B (2). The strain RK97-56 which produced the inhibitors was identified as Nocardia sp. by chemotaxonomic analyses, and the purification of the inhibitors was guided by their anti-angiogenic activities. PC-766B' (1) and PC-766B (2) exhibited potent inhibitory activities towards endothelial cell migration stimulated by the vascular endothelial growth factor (VEGF).

• Korean Journal of Acupuncture
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• 제26권2호
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• pp.27-38
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• 2009

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease, principally characterized by synovial inflammation of the joints. We previously reported the effect of acupuncture for RA, but the mechanism is still unclear. Various factors such as oxidative stress and angiogenesis were involved in the pathogenesis of RA, and recently, it has also been reported that cytokines also play a major role in RA. Thus, we investigated whether acupuncture could induce any changes in the levels of cytokines including vascular endothelial growth factor (VEGF), angiogenin and epidermal growth factor (EGF) as well as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and rheumatoid factor (RF) in the sera of RA patients. Methods: The forty three patients who met the American College of Rheumatology (ACR) criteria for RA recruited. The acupuncture group (n=21) underwent 14 sessions of partially individualized acupuncture treatment for 6 weeks, and the control group had no treatment (n=13) over the same periods. We evaluated ESR, CRP and RF. In addition, to find out the mechanism of acupuncture, we assessed the changes of the cytokine activities using protein cytokine array in the sera of the patients. Results: Acupuncture significantly decreased the levels of ESR and CRP, but RF were not changed after 6-week acupuncture treatments. Moreover, acupuncture reduced the levels of VEGF, angiogenin and EGF in the sera of the patients. Interestingly, they were related with angiogenesis, which is an important process in the pathogenesis of RA. The levels of oncostatin, interleukin(IL)-$1{\alpha}$, IL-8, leptin, monocyte chemotactic protein-1, macrophage-derived chemokine, macrophage inflammatory proteins-1, platelet-derived growth factor BB and RANTES were not changed significantly. Conclusions: The effect of acupuncture for reliving RA symptoms can be partially explained by inhibition of angiogenesis factors in the sera of the RA patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4453-4458
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• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• Archives of Plastic Surgery
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• 제40권3호
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• pp.181-186
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• 2013

Background Partial or complete necrosis of a skin flap is a common problem. Polydeoxyribonucleotide (PDRN) can be extracted from trout sperm and used as a tissue repair agent. The aim of this study was to investigate whether PDRN could improve the survival of random pattern skin flaps in rats. Methods Twenty-two male Sprague-Dawley rats were randomly divided into two groups: the PDRN treatment group (n=11) and the control group (n=11). Caudally pedicled random pattern skin flaps were elevated on their dorsal skin and resutured. The treatment group received daily intraperitoneal administration of PDRN (8 mg/kg/day), and the control group received fluid vehicle (NaCl 0.9%, 8 mg/kg/day) from day 0 to day 6. On day 7, the flap survival was evaluated and the harvested tissue surrounding the demarcation line of the necrotic area was stained with H&E, anti-rat vascular endothelial cell growth factor (VEGF) antibody, and PECAM-1/CD31 antibody. Results The average necrotic area of the flap in the PDRN group was significantly smaller when compared with that of the control group. Histologic and immunohistochemical evaluation showed that granulation thickness score and VEGF-positive staining cells were marked higher in the PDRN group than in the control group. PECAM-1/CD31-positive microvascular densities were significantly higher in the PDRN group when compared with the control group. Conclusions This study confirms that PDRN improves the survival of random pattern skin flaps in rats. These results may represent a new therapeutic approach to enhancing flap viability and achieving faster wound repair.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권3호
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• pp.197-205
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• 2007

Angiogenesis is a essential part for bone formation and bone fracture healing. Vascular endothelial growth factor (VEGF), one of the most important molecules among many angiogenic factors, is a specific mitogen for vascular endothelial cells. VEGF-mediated angiogenesis is required for bone formation and repair. However, the effect of VEGF on osteoblastic cells during osteogenesis is still controversial. In recent days, substantial progress have been made toward developing tissue-engineered alternatives to autologous bone grafting for maxillofacial bony defects. Periosteum has received considerable interest as a better source of adult stem cells. Periosteum has the advantage of easy harvest and contains various cell types and progenitor cells that are able to differentiate into a several mesenchymal lineages, including bone. Several studies have reported the bone formation potential of periosteal cells, however, the correlation between VEGF signaling and cultured human periosteal cell-derived osteogenesis has not been fully investigated yet. The purpose of this study was to examine the correlation between VEGF signaling and cultured human periosteal-derived cells osteogenesis. Periosteal tissues of $5\;{\times}\;20\;mm$ were obtained from mandible during surgical extraction of lower impacted third molar from 3 patients. Periosteal-derived cells were introduced into the cell culture and were subcultured once they reached confluence. After passage 3, the periosteal-derived cells were further cultured for 42 days in an osteogenic inductive culture medium containing dexamethasone, ascorbic acid, and ${\beta}-glycerophosphate$. We evaluated the alkaline phosphatase (ALP) activity, the expression of Runx2 and VEGF, alizarin red S staining, and the quantification of osteocalcin and VEGF secretion in the periosteal-derived cells. The ALP activity increased rapidly up to day 14, followed by decrease in activity to day 35. Runx2 was expressed strongly at day 7, followed by decreased expression at day 14, and its expression was not observed thereafter. Both VEGF 165 and VEGF 121 were expressed strongly at day 35 and 42 of culture, particularly during the later stages of differentiation. Alizarin red S-positive nodules were first observed on day 14 and then increased in number during the entire culture period. Osteocalcin and VEGF were first detected in the culture medium on day 14, and their levels increased thereafter in a time-dependent manner. These results suggest that VEGF secretion from cultured human periosteal-derived cells increases along with mineralization process of the extracellular matrix. The level of VEGF secretion from periosteal-derived cells might depend on the extent of osteoblastic differentiation.

• 생명과학회지
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• 제33권9호
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• pp.703-712
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• 2023

기존 혈관에서 새로운 혈관을 형성하는 혈관 신생은 혈관 신생 조절인자에 의해 조절되는 다단계 과정이며 배아 발달, 만성 염증 및 상처 복구를 포함한 다양한 생리학적 과정에 필수적이다. 혈관 신생의 조절장애는 암, 자가 면역 질환, 류마티스 관절염, 심혈관 질환 및 상처 치유 지연과 같은 많은 질병을 유발한다. 그러나 효과적인 혈관신생 억제 약물은 제한되어 있으며, 최근 연구에서는 천연 자원에서 잠재적인 약물후보를 식별하는 데 중점을 두고 있다. 예를 들어, 해양 천연물은 항암, 항산화, 항염증, 항바이러스 및 상처 치유 효과를 입증했다. 따라서 본 연구에서는 톳(갈조류) 추출물의 혈관 신생 억제 효과를 확인했습니다. H. fusiformis 추출물은 인간 제대 정맥 내피 세포(HUVECs)에서 세포 이동, 침윤 및 관 형성을 억제하며, 동시에 Matrigel 겔 플러그 분석을 통해 생체 내 혈관 신생을 억제를 확인했다. 또한, 톳 추출물 처리 후 VEGF, Erk, Akt의 활성이 감소하는 것을 확인했다. 이 결과를 토대로 H. fusiformis 추출물이 in vitro 및 in vivo 혈관 신생을 억제함을 시사한다.

• 한국축산식품학회지
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• 제44권1호
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• pp.204-215
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• 2024

This study was designed to examine the effect of Lactilactobacillus curvatus LB-P9 on hair regeneration. The treatment of LB-P9 conditioned medium increased the proliferation of both hair follicle dermal papilla cells and hair germinal matrix cells (hGMCs). Moreover, the expression levels of hair growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 7 were significantly elevated in hGMCs co-cultured with LB-P9. After time-synchronized depilation, mice were orally administered with either 4×10⁷ colony forming unit (CFU) of LB-P9 (low dose) or 4×10⁸ CFU of LB-P9 (high dose), once daily for 4 weeks. Compared with the vehicle (phosphate-buffered saline)-administrated group, the LB-P9-treated groups exhibited accelerated hair regrowth rate and enhanced hair thickness in a dose-dependent manner. Supporting this observation, both hair follicle numbers and the dermal thickness in skin tissues of the LB-P9-treated groups were increased, compared to those of the vehicle-treated group. These results might be explained by the increased level of β-catenin and number of hair follicle stem cells (CD34⁺ CD49f⁺ cells) in the skin tissues of mice administered with LB-P9, compared to the vehicle-treated mice. Also, increased serum levels of hair growth factors such as VEGF and insulin-like growth factor-1, and superoxide dismutase were found in the LB-P9-treated groups, compared to those of the vehicle-treated group. Taken together, these results might demonstrate that the oral administration of LB-P9 promotes hair regeneration by the enhancement of dermal papilla proliferation through the stimulation of hair growth factor production.

• 약학회지
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• 제54권2호
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• pp.102-105
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• 2010

Our previous results showed that hypoxia inducible factor-1 (HIF-1) activated estrogen receptor (ER) in the absence of ligand. In this study, we have studied the effect ER overexpression on the activation of HIF-1. ER overexpression induced transcription activation of hypoxia response element driven luciferase and vascular endothelial growth factor. As a negative control, the effect of ER on androgen receptor response element was used. Our result indicate that the two ER$\alpha$ and HIF-1 signaling pathways shares part of the activation pathway.