Silibinin Inhibits Angiogenesis via Flt-1, but not KDR, Receptor Up-Regulation1

Yang, Shung‐Haur; Lin, Johnson; Huang, Chun-Ta; Chen, Wei‐Shone; Li, Shih-Yun; Chiu, Jen‐Hwey

doi:10.1016/j.jss.2005.04.042

Cited by 47 publications

(32 citation statements)

References 33 publications

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“…Angiogenesis was analyzed using Image-Pro Plus software™ (version 4.5) at this program we calculate the vascular density index (VDI). VDI represents the number of intersections made by blood vessels (arterioles and venules) with a square grid containing nine smaller squares superimposed on the micrographs (YANG et al, 2005). Vessels were counted three times in random quadrants to obtain an average of vessels per mm² of each photograph.…”

Section: Gross Evaluation Of Angiogenesis In Cammentioning

confidence: 99%

Tissue damage and embryonic malformation induced by aqueous extract of Pteridium aquilinum on chorioallantoic membrane of chick embryo (CAM)

Leitolis¹,

Souza²,

Freitas³

et al. 2017

SCA

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The aim of this study was evaluate the effects of Bracken fern (BF) (Pteridium aquilinum (L.) Kuhn.) on biological systems. When consumed by animals can cause acute intoxication, hematuria, biochemistry alterations and cancer. To humans the toxicity is associated with its intake on contaminated ground water or milk and inhalation of its spores. In order to check the BF aqueous extract (AEB) deleterious effects on animals blood vessels system, chick embryo chorioallantoic membrane (CAM) was used. It were applying on CAM 0.1, 0.5, 1, 5, 10 e 15 µg/mL of AEB and saline as control. The angiogenesis was analyzed and the vascular density index (VDI) calculated. The CAM samples were prepared and stained with H&E to evaluation of microvessels, Masson's trichrome to characterize collagen and fibrin deposition and Picro-sirius used to evaluate collagen using polarized light. Also the morphological aspects of embryos were analysed. We observe on the results of neovascularization that AEB did not change significantly the number of vessels/mm², however, membranes treated with AEB (5 or 10 µg/ mL) exhibit opacity and tissue fibrosis, both signs of inflammation. Histological analysis with Masson's trichrome and picro-sirius on tissues exposed to AEB respectively has shown increased collagen fibers and presence of fibrilar collagen. The embryos exposed to concentrations of 5 or 10 μg/mL AEB, showed changes as poor face formation and poor closing of abdominal wall. The highest concentration of AEB (15 μg/mL) was lethal to embryos. Although significant effects on the CAM's vasculature has not observed, tissue aggression was detected, a desmoplasia (an extensive inflammatory signal triggered by tissue injury), changes caused on embryos as well as the presence of toxic substances in the AEB show us an important and deleterious pathway of this bracken fern extract on its intoxicants effects on humans and animals, and even cancer or the death of animals. ResumoO foco principal desse estudo foi avaliar os efeitos do extrato aquoso de Samambaia (EAS) (Pteridium aquilinum (L.) Kuhn) sobre sistemas biológicos. A ingestão das folhas de Samambaia pode provocar intoxicação aguda, hematúria, alterações bioquímicas e câncer se consumida por animais. Em humanos também pode provocar intoxicação ao ser ingerida com água ou leite contaminados e pela inalação de seus esporos. Considerando os efeitos danosos provocados pelo consumo dessa planta esse estudo analisou a ação do EAS sobre um sistema de vasos sanguíneos, a membrana corioalantóide (MCA) de embrião de galinha. Sobre a MCA foram aplicados 0,1, 0,5, 1, 5, 10 e 15 µg/mL de EAS, salina como controle. A angiogênese foi analisada e o índice de densidade vascular (IDV) calculado. Amostras da CAM foram coradas com H&E para avaliação de microvasos, Tricrômico de Masson para caracterização de colágeno e deposição de fibrina e Picro-sirius para analisar o colágeno através de luz polarizada. Os aspectos morfológicos dos embriões também foram analisados. Os resultados da neovascularização mos...

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Section: Gross Evaluation Of Angiogenesis In Cammentioning

confidence: 99%

Tissue damage and embryonic malformation induced by aqueous extract of Pteridium aquilinum on chorioallantoic membrane of chick embryo (CAM)

Leitolis¹,

Souza²,

Freitas³

et al. 2017

SCA

View full text Add to dashboard Cite

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“…Silibinin-mediated reduction in colorectal carcinoma proliferation and concomitant increase in apoptosis were associated with inhibition of ERK1/2 and Akt (43). Silibinin-mediated angiogenesis inhibition was associated with decreased VEGF, cyclooxygenase (COX), hypoxiainducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), nitrotyrosine and nitrite levels, and an increased VEGFR-1 (Flt-1) expression (41,(43)(44)(45). Silibinin inhibited CDK8 and β-catenin signaling which inhibited SW480 tumor growth (46) and initiated an autophagic-mediated survival response in SW480 and SW620 cells (47).…”

Section: Broad Spectrum Cancer Chemopreventive Efficacy Of Silibininmentioning

confidence: 99%

Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer

Ting

Deep

Agarwal

2013

AAPS J

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Abstract. Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged deleterious effects on quality of patient life. Prostate cancer chemoprevention is one potential avenue to alleviate these burdens. It is a regime whereby long-term treatments are intended to prevent or arrest cancer development, in contrast to more direct intervention upon disease diagnosis. Based on this intention, cancer chemoprevention generally focuses on the use of nontoxic chemical agents which are well-tolerated for prolonged usage that is necessary to address prostate cancer's multistage and lengthy period of progression. One such nontoxic natural agent is the flavonoid silibinin, derived from the milk thistle plant (Silybum marianum), which has ancient medicinal usage and potent antioxidant activity. Based on these properties, silibinin has been investigated in a host of cancer models where it exhibits broad-spectrum efficacy against cancer progression both in vitro and in vivo without noticeable toxicity. Specifically in prostate cancer models, silibinin has shown the ability to modulate cell signaling, proliferation, apoptosis, epithelial to mesenchymal transition, invasion, metastasis, and angiogenesis, which taken together provides strong support for silibinin as a candidate prostate cancer chemopreventive agent.

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“…We reviewed here some of the most investigated phytocompounds concerning the results obtained on all the three experimental models ( Table 1). Reduction of MMP9, COX-2 and VEGF [61] dose-dependent suppressive on angiogenesis [62] A/J mice with Urethaneinduced lung tumors Inhibition of new microvessels formation; Decreased levels of IL-1α,-6, -9, -13, -16, IFN-γ and TNF-α [63] Natural Products and Cancer Drug Discovery …”

Section: Phytocompounds Targeting Cancer Angiogenesis: In Vitro On Tmentioning

confidence: 99%

Phytocompounds Targeting Cancer Angiogenesis Using the Chorioallantoic Membrane Assay

Avram¹,

Ghiulai²,

Pavel³

et al. 2017

Natural Products and Cancer Drug Discovery

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Cancer is the second cause of mortality worldwide. Angiogenesis is an important process involved in the growth of primary tumors and metastasis. New approaches for controlling the cancer progression and invasiveness can be addressed by limiting the angiogenesis process. An increasingly large number of natural compounds are evaluated as angiogenesis inhibitors. The chorioallantoic membrane (CAM) assay represents an in vivo attractive experimental model for cancer and angiogenesis studies as prescreening to the murine models. Since the discovery of tumor angiogenesis, the CAM has been intensively used in cancer research. The advantages of this in vivo technique are in terms of low time-consuming, costs, and a lower number of sacrificed animals. Currently, a great number of natural compounds are being investigated for their effectiveness in controlling tumor angiogenesis. Potential reducing of angiogenesis has been investigated by our group for pentacyclic triterpenes, in various formulations, and differences in their mechanism were registered.This chapter aims to give an overview on a number of phytocompounds investigated using in vitro, murine models and the chorioallantoic membrane assay as well as to emphasize the use of CAM assay in the study of natural compounds with potential effects in malignancies.

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Silibinin Inhibits Angiogenesis via Flt-1, but not KDR, Receptor Up-Regulation1

Cited by 47 publications

References 33 publications

Tissue damage and embryonic malformation induced by aqueous extract of Pteridium aquilinum on chorioallantoic membrane of chick embryo (CAM)

Tissue damage and embryonic malformation induced by aqueous extract of Pteridium aquilinum on chorioallantoic membrane of chick embryo (CAM)

Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer

Phytocompounds Targeting Cancer Angiogenesis Using the Chorioallantoic Membrane Assay

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