The Effect of Myricetin Flavonoid on the Expression of Fyn Gene in Melanoma Cells (A375)

Fereshte Abdolmaleki, S. Moghbelinejad, Hossein Ahmadpour-Yazdi
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Abstract

Background: Malignant melanoma as one of the most common cancers is currently spreading worldwide. Regarding after-effect of advanced treatments, using natural products has attracted much attention. Flavonoids, polyphenol compounds rich in diet, are being considered for their therapeutic preventive features. Fyn gene, a member of the protein tyrosine kinase oncogene family, has become an important target for therapy goals. Objectives: The aim of this study was to assess Fyn gene expression after treatment of melanoma cells with myricetin. Methods: In this study, the melanoma cells were treated with different concentrations of myricetin (0 to 100 �M) and their viability was determined by the methylthiazolyl diphenyl-tetrazolium bromide (MTT) assay, also the expression of Fyn gene in treated cells with selected concentrations of myricetin (0, 20, 40, 50, and 60 �M) was detected by real time quantitative polymerase chain reaction (qPCR). Results: The current investigation showed that treatment of A375 melanoma cells with the dietary flavonoid myricetin (3, 5, 7- trihydroxy-2-(3, 4, 5,-trihydroxy phenyl)-4- chromenone), resulted in decreased cell viability and increased expression of Fyn gene. The MTT assay analysis of exposed cells with different concentrations of myricetin showed that up to 25 �Mof myricetin had no cytotoxicity effect on A375 cells, also with increasing of myricetin concentration, the repression of cell proliferation developed as well. Conclusions: Real time qPCR analysis of Fyn expression in exposed cells with various concentration of myricetin leads to overexpression of this gene, dose dependently. Through this research, it was determined that myricetin with its anti-proliferative potential could suppress the development of cancer cells. On the other hand, since Fyn kinase could be involved in tumorigenesis of some cancer cells, it could be concluded that myricetin could effect the carcinogenicity of Fyn function in melanoma cells. Keywords: Melanoma, A375, Myricetin, Fyn Gene
杨梅素黄酮对黑色素瘤细胞(A375) Fyn基因表达的影响
背景:恶性黑色素瘤是目前世界范围内最常见的癌症之一。关于高级护理的后效,使用天然产品已经引起了人们的关注。黄酮类化合物是一种富含膳食的多酚化合物,被认为具有治疗和预防作用。Fyn基因是蛋白酪氨酸激酶癌基因家族的一员,已成为治疗目标的重要靶点。目的:本研究的目的是评估用杨梅素治疗黑色素瘤细胞后Fyn基因的表达。方法:用不同浓度的杨梅素(0 ~ 100 μ M)处理黑色素瘤细胞,采用甲基噻唑基二苯基溴化四唑(MTT)法检测细胞活力,并采用实时定量聚合酶链反应(qPCR)检测不同浓度杨梅素(0、20、40、50、60 μ M)处理细胞中Fyn基因的表达。结果:目前的研究表明,用膳食黄酮类杨梅素(3,5,7 -三羟基-2-(3,4,5,-三羟基苯基)-4-铬酮)处理A375黑色素瘤细胞,导致细胞活力下降,Fyn基因表达增加。不同浓度杨梅素对A375细胞的MTT分析表明,当杨梅素浓度达到25 μ m时,对A375细胞没有细胞毒性作用,且随着杨梅素浓度的增加,细胞增殖也受到抑制。结论:实时qPCR分析不同浓度杨梅素暴露的细胞中Fyn的表达导致该基因过表达,且呈剂量依赖性。通过本研究,确定杨梅素具有抗增殖潜能,可以抑制癌细胞的发展。另一方面,由于Fyn激酶可能参与某些癌细胞的肿瘤发生,因此可以得出结论,杨梅素可能影响Fyn功能在黑色素瘤细胞中的致癌性。关键词:黑色素瘤,A375,杨梅素,Fyn基因
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