• 제목/요약/키워드: Cancer angiogenesis

검색결과 404건 처리시간 0.022초

Anthocyanins from the Fruit of Vitis Coignetiae Pulliat Inhibit TNF-Augmented Cancer Proliferation, Migration, and Invasion in A549 Cells

  • Lu, Jing Nan;Panchanathan, Radha;Lee, Won Sup;Kim, Hye Jung;Kim, Dong Hoon;Choi, Yung Hyun;Kim, GonSup;Shin, Sung Chul;Hong, Soon Chan
    • Asian Pacific Journal of Cancer Prevention
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    • 제18권11호
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    • pp.2919-2923
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    • 2017
  • Objective: Anthocyanins belong to a class of flavonoids, exhibiting antioxidant and anti-inflammatory actions have been reported to have anti-cancer effects. Here, we investigated whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in human lung cancer A549 cells, which are critically involved in cancer metastasis. Methods: We used anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) which has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. We have performed cell proliferation assays, cell invasion assay, gelatin zymography, wound healing assay and western blotting to examine whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in A549 cells. Result: AIMs did not inhibit cancer cell proliferation on A549 cells. Also, AIMs suppressed cancer migration, and invasion by supressing MMP-2 and MMP-9 expression. The Immuno-blotting results also revealed that AIMs suppressed the proteins involved in cancer proliferation (COX-2, C-myc, cyclin D1), migration and invasion (MMP-2, MMP-9), anti-apoptosis (XIAP, and c-IAP2), adhesion and angiogenesis (ICAM-1, VEGF). Conclusion: This study demonstrates that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat inhibit cancer proliferation, cancer migration, and invasion that is involve in cancer-metastasis. This study provides evidence that AIMs might have anti-cancer effects on human lung cancer.

활락효영단합인삼양위탕(活絡效靈丹合人蔘養胃湯)이 혈관신생(血管新生) 억제(抑制)에 미치는 영향(影響) (Effect of Whalakyuoleyng-dan plus Yinsamyangwui-tang on Anti-angionesis)

  • 고기완;박준혁;강희;김성훈;유영법;심범상;최승훈;안규석
    • 대한한방종양학회지
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    • 제7권1호
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    • pp.77-97
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    • 2001
  • Anti-angiogenesis is one of therapies which have been high-lightened on the research of cancer treatment. Anti-angiogenesis means that new blood vessels are created from a existing capillary tube and it is a important process on metastasis and permeation when cancer is created or formed. Since angiogenesis have been under research, a complete recovery oriented treatment against cancer have been suggested blocking metastasis, delaying the growth of cancer cell, and blocking the supply of oxygen and nutritive substance through the web of blood vessels. Until now, there are several anti-angiogenesis, which have been known to the public, such as thalidomide, angiostatin, endostatin, 2-methoxyestradiol, TNP-470, and marimastat, etc. Additionally, 17 clinical testing projects about anti-angiogenesis are on the process in NCI(National Cancer Institute). Especially, TNP-470 showed effectiveness against cancer on clinical testing after finishing animal testing. Based on existing researches showing that Yinsamyangwui-tang is effective to strengthening body resistance and Whallakhyolenyng-dan effects cells on the inside of blood vessel because Whallakhyolenyng- dan restrains cell adhesion during the restraining period of a blood vessel, I tried to research the effect of Whalakhyolenyng-dan plus Yinsamyangwui-tang on angiogenesis. I made a conclusion putting into operation through using SK-Hep-1 (KCLB 30052), A549(KCLB 10185), AGS(KCLB 21739), and BCE(Bovine Capillary Endothelial Cell). Followings are the results of my experimental research: 1. According to the researching results of anti-cancer activation against cancer cell, Whallkhyoleyng dan plus Yinsamyangwui-tang decreased the number of cancer cells -- While injecting $600{\mu}g/ml$, injected groups decreased 3.1% more comparing with the contrastive group of SK-Hep-1, 49.7% more comparing with the contrastive group of A549, and 31.0% more comparing with the contrastive group of AGS. 2. According to the researching results of DNA composition effect between BCE and cancer cell, Whallakhyoleyng-dan plus Yinsamyangwui-tang reduced the rate of SK-Hep-1 synthesis inhibition by 59.1% at $600{\mu}g/ml$ intensity comparing with contrastive group; for A549, 72.6%; for AGS, 6.1%, for BCE, 28.9%. 3. According to the researching results about the effect of BCE cell to angiogenesis, angiogenesis was restrained at $400{\mu}g/ml$ intensity during 18 hours observation. 4. In the case of aortic ring assay, the half level of angiogenesis was reduced comparing with the contrastive group while injecting with $400{\mu}g/ml$ intensity; with $800{\mu}g/ml$, under 10% comparing with contrastive group; and with $1600{\mu}g/ml$, complete restrain. According to the above results, Whallakhyoleyng-dan plus Yinsamyangwui-tang was proved to have an anti-angiogenetic effects.

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Development of Angiogenesis Inhibitors: an Analysis of the Patent Literatures

  • Sohn, Eun-Soo;Sohn, Eun-Hwa
    • 대한의생명과학회지
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    • 제17권2호
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    • pp.95-104
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    • 2011
  • The development of a general appreciation for the central role of angiogenesis in cancer growth and metastasis and other disease status has led to a wide range of new therapeutic strategies. This paper reviews the domestic and international trends through technology, marketing and patent information analysis dealing with anti-angiogenic agents. This analytical research has led to the identification of new targets associated with angiogenesis, leading to the development of an extensive number of preclinical screening of antiangiogenetic agents.

VEGF-VEGFR Signals in Health and Disease

  • Shibuya, Masabumi
    • Biomolecules & Therapeutics
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    • 제22권1호
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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.

Novel Anti-Angiogenic and Anti-Tumour Activities of the N-Terminal Domain of NOEY2 via Binding to VEGFR-2 in Ovarian Cancer

  • Rho, Seung Bae;Lee, Keun Woo;Lee, Seung-Hoon;Byun, Hyun Jung;Kim, Boh-Ram;Lee, Chang Hoon
    • Biomolecules & Therapeutics
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    • 제29권5호
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    • pp.506-518
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    • 2021
  • The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3'-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the three-dimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

MMPP is a novel VEGFR2 inhibitor that suppresses angiogenesis via VEGFR2/AKT/ERK/NF-κB pathway

  • Na-Yeon Kim;Hyo-Min Park;Jae-Young Park;Uijin Kim;Ha Youn Shin;Hee Pom Lee;Jin Tae Hong;Do-Young Yoon
    • BMB Reports
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    • 제57권5호
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    • pp.244-249
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    • 2024
  • Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.

Expression of Bax and Bcl-2 in Tumour Cells and Blood Vessels of Breast Cancer and their Association with Angiogenesis and Hormonal Receptors

  • Jaafar, Hasnan;Abdullah, Suhaila;Murtey, Mogana Das;Idris, Fauziah M.
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.3857-3862
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    • 2012
  • A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

Hizikia fusiformis 추출물의 in vitro 및 in vivo에서 혈관신생 감소 연구 (Hizikia Fusiformis Hexane Extract Decreases Angiogenesis in Vitro and in Vivo)

  • 제갈명은;한유선;박시영;이지혁;이의연;김영진
    • 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.

Anti-proliferative and angio-suppressive effect of Stoechospermum marginatum (C. Agardh) Kutzing extract using various experimental models

  • Vinayak, Rashmi;Puttananjaiah, Shilpa;Chatterji, Anil;Salimath, Bharati
    • Nutrition Research and Practice
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    • 제8권4호
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    • pp.377-385
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    • 2014
  • BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.