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Angiogenesis Aug 2020Breast cancer is one of the most common cancers worldwide with a rising incidence, and is the leading cause of cancer-related death among females. Angiogenesis plays an...
Breast cancer is one of the most common cancers worldwide with a rising incidence, and is the leading cause of cancer-related death among females. Angiogenesis plays an important role in breast cancer growth and metastasis. In this study, we identify decylubiquinone (DUb), a coenzyme Q analog, as a promising anti-breast cancer agent through suppressing tumor-induced angiogenesis. We screened a library comprising FDA-approved drugs and found that DUb significantly inhibits blood vessel formation using in vivo chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. DUb was further identified to inhibit angiogenesis in the rat aortic ring and Matrigel plug assay. Moreover, DUb was found to suppress breast cancer growth and metastasis in the MMTV-PyMT transgenic mouse and human xenograft tumor models. To explore whether the anticancer efficacy of DUb was directly corrected with tumor-induced angiogenesis, the MDA-MB-231 breast cancer assay on the CAM was performed. Interestingly, DUb significantly inhibits the angiogenesis of breast cancer on the CAM. Brain angiogenesis inhibitor 1 (BAI1), a member of the G protein-coupled receptor (GPCR) adhesion subfamily, has an important effect on the inhibition of angiogenesis. Further studies demonstrate that DUb suppresses the formation of tubular structures by regulating the reactive oxygen species (ROS)/p53/BAI1 signaling pathway. These results uncover a novel finding that DUb has the potential to be an effective agent for the treatment of breast cancer by inhibiting tumor-induced angiogenesis.
Topics: Animals; Breast Neoplasms; Chick Embryo; Female; Humans; MCF-7 Cells; Neoplasm Metastasis; Neoplasm Proteins; Neovascularization, Pathologic; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Signal Transduction; Tumor Suppressor Protein p53; Ubiquinone
PubMed: 32020421
DOI: 10.1007/s10456-020-09707-z -
Rheumatology (Oxford, England) Feb 1999Indices of angiogenesis are increased in synovia from patients with arthritis, and vascular proliferation may contribute to the pathogenesis of synovitis, pannus growth,... (Review)
Review
Indices of angiogenesis are increased in synovia from patients with arthritis, and vascular proliferation may contribute to the pathogenesis of synovitis, pannus growth, bone and cartilage destruction, and osteophyte formation. Pharmacological inhibition of angiogenesis therefore has potential as a therapeutic strategy in human arthritis. However, vascular growth is also essential for normal development, female reproduction and tissue repair. Selective inhibition of undesirable angiogenesis requires an understanding of the different regulatory mechanisms in pathological and physiological angiogenesis. This review outlines the evidence that the rate of angiogenesis is increased in the inflamed human synovium, and possible approaches to, and consequences of, the modulation of vascular growth.
Topics: Arthritis; Female; Humans; Male; Muscle, Smooth, Vascular; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 10342621
DOI: 10.1093/rheumatology/38.2.103 -
Cold Spring Harbor Perspectives in... Mar 2023Angiogenesis, the growth of new blood vessels, plays a critical role in tissue repair and regeneration, as well as in cancer. A paradigm shift is emerging in our... (Review)
Review
Angiogenesis, the growth of new blood vessels, plays a critical role in tissue repair and regeneration, as well as in cancer. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving mediators (SPMs), including resolvins. Angiogenesis and the resolution of inflammation are critical interdependent processes. Disrupted inflammation resolution can accelerate tumor growth, which is angiogenesis-dependent. SPMs, including resolvins and lipoxins, inhibit physiologic and pathological angiogenesis at nanogram concentrations. The failure of resolution of inflammation is an emerging hallmark of angiogenesis-dependent diseases including arthritis, psoriasis, diabetic retinopathy, age-related macular degeneration, inflammatory bowel disease, atherosclerosis, endometriosis, Alzheimer's disease, and cancer. Whereas therapeutic angiogenesis repairs tissue damage (e.g., limb ischemia), inhibition of pathological angiogenesis suppresses tumor growth and other non-neoplastic diseases such as retinopathies. Stimulation of resolution of inflammation via pro-resolving lipid mediators promotes the repair of tissue damage and wound healing, accelerates tissue regeneration, and inhibits cancer. Here we provide an overview of the mechanisms of cross talk between angiogenesis and inflammation resolution in chronic inflammation-driven diseases. Stimulating the resolution of inflammation via pro-resolving lipid mediators has emerged as a promising new field to treat angiogenic diseases.
Topics: Humans; Inflammation; Atherosclerosis; Ischemia; Lipids; Neovascularization, Pathologic; Inflammation Mediators
PubMed: 35817542
DOI: 10.1101/cshperspect.a041172 -
Angiogenesis Nov 2023Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These...
Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These different modes of angiogenesis involve, for example, increasing microvasculature density by sprouting of endothelial cells, splitting of vessels to increase vascular surface area by intussusceptive angiogenesis, fusion of capillaries to increase blood flow by coalescent angiogenesis, and the recruitment of non-endothelial cells by vasculogenic mimicry. The recent reporting on coalescent angiogenesis as a new mode of vessel formation warrants a brief overview of angiogenesis mechanisms to provide a more complete picture. The journal Angiogenesis is devoted to the delineation of the different modes and mechanisms that collectively dictate blood vessel formation, inhibition, and function in health and disease.
Topics: Neovascularization, Physiologic; Endothelial Cells; Capillaries; Morphogenesis
PubMed: 37640982
DOI: 10.1007/s10456-023-09895-4 -
The Journal of Investigative... Dec 2000In order to grow beyond minimal size and to metastasize, tumors need to induce the growth of new blood vessels (angiogenesis). Whereas in normal tissues, vascular... (Review)
Review
In order to grow beyond minimal size and to metastasize, tumors need to induce the growth of new blood vessels (angiogenesis). Whereas in normal tissues, vascular quiescence is maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli, tumor angiogenesis is induced by increased secretion of angiogenic factors and/or by downregulation of angiogenesis inhibitors. Recent evidence suggests vascular endothelial growth factor (VEGF) as the major tumor angiogenesis factor, promoting tumor growth, invasion, and metastasis. Conversely, blocking of VEGF function inhibits angiogenesis and suppresses tumor growth in vivo. Newly identified members of the VEGF family of angiogenesis factors include placental growth factor, VEGF-B, VEGF-C, and VEGF-D, and show overlapping binding patterns to specific endothelial cell receptors. VEGF-C appears to play a major role as a lymphangiogenesis factor and as a growth factor for Kaposi's sarcoma. In contrast, endogenous inhibitors prevent blood vessel growth in normal tissues. In particular, thrombospondin-1 (TSP-1) and TSP-2 are expressed in normal skin and, when introduced into squamous cell carcinomas, potently inhibit malignant tumor growth via inhibition of tumor angiogenesis.
Topics: Animals; Endothelial Growth Factors; Humans; Lymphokines; Neovascularization, Pathologic; Skin Neoplasms; Thrombospondin 1; Thrombospondins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 11147670
DOI: 10.1046/j.1087-0024.2000.00003.x -
Cancer Biology & Therapy Oct 2005Hypoxia is an important phenomenon in the tumor microenvironment. Hypoxic tumors are more aggressive and resistant to anti-neoplastic treatments. HIF-1alpha plays a... (Review)
Review
Hypoxia is an important phenomenon in the tumor microenvironment. Hypoxic tumors are more aggressive and resistant to anti-neoplastic treatments. HIF-1alpha plays a major role in the response of tumors to hypoxia, and it is mainly responsible for the "angiogenic switch". HIF-1alpha contributes to tumor aggressiveness, invasiveness, and resistance to radiotherapy and chemotherapy. Targeting HIF-1alpha is an attractive strategy, with the potential for disrupting multiple pathways crucial for tumor growth. We review recent findings on the potential efficacy of small molecules to downregulate HIF-1alpha. These promising drugs inhibit HIF-1alpha synthesis or transcriptional activity by blocking a variety of steps in several different signaling pathways. Blocking HIF-1alpha activity should not only downregulate tumor angiogenesis, but also interfere with glycolytic metabolism and tumor cell growth. This strategy could also improve the efficiency of established tumor therapies.
Topics: Cell Hypoxia; Gene Targeting; Humans; Hypoxia-Inducible Factor 1; Models, Biological; Neovascularization, Pathologic
PubMed: 16294030
DOI: 10.4161/cbt.4.10.2195 -
Journal of Experimental & Clinical... Oct 2018Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding...
BACKGROUND
Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding its anti-tumor mechanism still remain unclear.
METHODS
Cell viability and proliferation were measured by CCK8 and CFSE dilution assay. The localization of p50/p65 or cytochrome c was determined using confocal immunofluorescence. Streptavidin-agarose pulldown or ChIP assays were used to detect the binding of multiple transactivators to COX-2 promoter. The promoter activity was examined by a dual-Luciferase reporter assay. The functions of Andro on COX-2-mediated angiogenesis were also investigated using human HUVEC cells through tube formation and spheroids sprouting assay. The in vivo anti-tumor efficacy of Andro was analyzed in xenografts nude mice.
RESULTS
The results indicated that Andro could significantly inhibit the proliferation of human breast cancers, and suppress COX-2 expression at both protein and mRNA levels. Furthermore, Andro could dose-dependently inhibit COX-2-mediated angiogenesis in human endothelial cells. We have also found that Andro significantly promoted the activation of cytochrome c and activated caspase-dependent apoptotic signaling pathway. Our further explorations demonstrated that Andro inhibited the binding of the transactivators CREB2, C-Fos and NF-κB and blocked the recruitment of coactivator p300 to COX-2 promoter. Moreover, Andro could effectively inhibit the activity of p300 histone acetyltransferase (HAT), thereby attenuating the p300-mediated acetylation of NF-κB. Besides, Andro could also dramatically inhibit the migration, invasion and tubulogenesis of HUVECs in vitro. In addition, Andro also exhibited effective anti-tumor efficacy as well as angiogenesis inhibition in vivo.
CONCLUSION
In current study, we explore the potential effects of Andro in suppressing breast cancer growth and tumor angiogenesis, as well as the precise mechanisms. This work demonstrated the potential anti-cancer effects of Andro, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Diterpenes; E1A-Associated p300 Protein; Female; Humans; Mice; Mice, Nude; Neovascularization, Pathologic; Signal Transduction; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays
PubMed: 30314513
DOI: 10.1186/s13046-018-0926-9 -
International Journal of Molecular... Sep 2020Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or...
BACKGROUND
Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient's further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study.
METHODS
Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed.
RESULTS
The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line.
Topics: Angiogenesis Inhibitors; Apoptosis; Cell Line; Cell Movement; Cell Proliferation; Endothelial Cells; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Plasma Gases
PubMed: 32993057
DOI: 10.3390/ijms21197098 -
Microcirculation (New York, N.Y. : 1994) Jan 2014Ample interest has been evoked in using placental angiogenesis as a target for the development of diagnosis tools and potential therapeutics for pregnancy complications... (Review)
Review
Ample interest has been evoked in using placental angiogenesis as a target for the development of diagnosis tools and potential therapeutics for pregnancy complications based on the knowledge of placental angiogenesis in normal and aberrant pregnancies. Although these goals are still far from reach, one would expect that two complementary processes should be balanced for therapeutic angiogenesis to be successful in restoring a mature and functional vascular network in the placenta in any pregnancy complication: (i) pro-angiogenic stimulation of new vessel growth and (ii) anti-angiogenic inhibition of vessel overgrowth. As the best model of physiological angiogenesis, investigations of placental angiogenesis provide critical insights not only for better understanding of normal placental endothelial biology but also for the development of diagnosis tools for pregnancy complications. Such investigations will potentially identify novel pro-angiogenic factors for therapeutic intervention for tissue damage in various obstetric complications or heart failure or anti-angiogenic factors to target on cancer or vision loss in which circulation needs to be constrained. This review summarizes the genetic and molecular aspects of normal placental angiogenesis as well as the signaling mechanisms by which the dominant angiogenic factor vascular endothelial growth factor regulates placental angiogenesis with a focus on placental endothelial cells.
Topics: Endothelial Cells; Female; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Placenta; Pregnancy; Vascular Endothelial Growth Factor A
PubMed: 23981199
DOI: 10.1111/micc.12093 -
Chinese Journal of Integrative Medicine Aug 2016Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells (LSECs) and formation...
Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells (LSECs) and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fifibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fifibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fifibrosis through inhibiting angiogenesis.
Topics: Drugs, Chinese Herbal; Esophageal and Gastric Varices; Hemorrhage; Humans; Liver Cirrhosis; Microcirculation; Neovascularization, Pathologic
PubMed: 27107572
DOI: 10.1007/s11655-016-2468-3