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      Quercetin inhibits angiogenesis-mediated human retinoblastoma growth by targeting vascular endothelial growth factor receptor

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          Abstract

          Retinoblastoma (RB) is the most common malignant intraocular cancer in teenagers, occurrence of which depends on the mutation of multiple genes. Among all the signaling pathways involved in the oncogenesis of RB, the process of angiogenesis has been demonstrated to be associated with the local invasive growth and metastasis of this cancer type. Quercetin (Que) is a typical flavonoid and has been reported to inhibit angiogenesis in various types of tumors. In the present study, the effect of Que on RB cells and angiogenesis of RB was evaluated. The human RB Y79 cell line was subjected to treatment with Que of various concentrations. Viability, invasion and migration ability and apoptosis of Y79 cells were subsequently measured to assess the effect of Que on RB cells. In addition, the expression of vascular endothelial growth factor receptor (VEGFR) was also quantified. It was revealed that Que inhibited RB cell growth and invasion in vitro in a dose-dependent manner, with 100 µM Que exhibiting the strongest inhibitory effect. In addition, Que downregulated the expression of VEGFR, which was an indicator of the blockade of angiogenesis in RB by targeting VEGF. The effect of Que on angiogenesis was also observed to be dose-dependent. The results of the present study indicated that Que may be a potential anti-RB therapy due to its anti-angiogenesis effect.

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          Most cited references28

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          Mutation and cancer: statistical study of retinoblastoma.

          A Knudson (1971)
          Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye. This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.
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            Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation.

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              Multitargeted cancer prevention by quercetin.

              Quercetin is an anti-oxidative flavonoid widely distributed in the plant kingdom. Phenolic hydroxyl groups at the B-ring and the 3-position are responsible for its free radical-scavenging activity. Quercetin is commonly present as a glycoside and is converted to glucuronide/sulfate conjugates during intestinal absorption and only conjugated metabolites are therefore found in circulating blood. Although metabolic conversion attenuates its biological effects, active aglycone may be generated from the glucuronide conjugates by enhanced beta-glucuronidase activity during inflammation. With respect to its relationship with molecular targets relevant to cancer prevention, quercetin aglycone has been shown to interact with some receptors, particularly an aryl hydrocarbon receptor, which is involved in the development of cancers induced by certain chemicals. Quercetin aglycone has also been shown to modulate several signal transduction pathways involving MEK/ERK and Nrf2/keap1, which are associated with the processes of inflammation and carcinogenesis. Rodent studies have demonstrated that dietary administration of this flavonol prevents chemically induced carcinogenesis, especially in the colon, whilst epidemiological studies have indicated that an intake of quercetin may be associated with the prevention of lung cancer. Dietary quercetin is, therefore, a promising agent for cancer prevention and further research is warranted.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                September 2017
                20 July 2017
                20 July 2017
                : 14
                : 3
                : 3343-3348
                Affiliations
                [1 ]Department of Ophthalmology, The Second Hospital of Shandong University, Jinan, Shandong 250000, P.R. China
                [2 ]Department of Emergency, Shandong Provincial Hospital, Jinan, Shandong 250000, P.R. China
                Author notes
                Correspondence to: Dr Han Zhang, Department of Ophthalmology, The Second Hospital of Shandong University, 247 Beiyuan Road, Jinan, Shandong 250000, P.R. China, E-mail: zhanhan2016@ 123456163.com
                Article
                OL-0-0-6623
                10.3892/ol.2017.6623
                5588034
                28927086
                afff31e3-4848-4126-bf57-af2ce48b1e30
                Copyright: © Song et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 15 March 2016
                : 14 February 2017
                Categories
                Articles

                Oncology & Radiotherapy
                quercetin,retinoblastoma,vascular endothelial growth factor,angiogenesis

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