Umbelliferone inhibits proliferation and metastasis via modulating cadherin/β-catenin complex-aided cell-cell adhesion in glioblastoma cells.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Wei Ma, Hangyu Shi, Xinya Dong, Yongqiang Shi, Luyi Zhang, Bin Jiang
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Abstract

Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumor malignancy in adults, accounting for nearly 50% of all gliomas. Current medications for GBM frequently lead to drug resistance.

Objectives: Umbelliferone (UMB) is found extensively in many plants and shows numerous pharmacological actions against inflammation, degenerative diseases and cancers. However, its anticancer effects on GBM cells have not yet been explored.

Material and methods: This research intended to assess the antitumor efficacy of UMB and the molecular mechanism of cell-cell adhesion proteins in human U-87 GBM cells. The cytotoxicity assay, intracellular reactive oxygen species (ROS), cell adhesion proteins, and cell apoptosis actions of UMB were assessed using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT), dichlorodihydrofluorescein diacetate (DCFH-DA), 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB), and western blot.

Results: The findings revealed that UMB reduced the proliferation of GBM cells and cell adhesion proteins, while augmenting apoptosis through the elevation of cellular ROS. Bcl-2 family protein levels of Bcl-2 and Bcl-XL were mitigated; conversely, the pro-apoptotic proteins Bad and Bim were elevated upon treatment with UMB in a quantity-dependent way. Furthermore, UMB-treated GBM cells suppressed N-cadherin, β-catenin, Slug, and matrix metalloproteinase 2 (MMP-2) expression, whereas they showed enhanced TIMP protein and E-cadherin levels.

Conclusions: Our findings suggest that UMB can prevent proliferation and metastasis and stimulate apoptosis in GBM cells.

umbellliferone通过调节钙粘蛋白/β-catenin复合物辅助胶质母细胞瘤细胞粘附抑制细胞增殖和转移。
背景:多形性胶质母细胞瘤(GBM)是成人中最具侵袭性的恶性脑肿瘤,占所有胶质瘤的近50%。目前治疗GBM的药物经常导致耐药性。目的:伞形花酮(UMB)广泛存在于多种植物中,具有多种抗炎症、退行性疾病和癌症的药理作用。然而,其对GBM细胞的抗癌作用尚未被研究。材料与方法:本研究旨在研究UMB对人U-87 GBM细胞的抗肿瘤作用及细胞-细胞粘附蛋白的分子机制。采用3-[4,5 -二甲基噻唑-2-酰基]- 2,5 -二苯基溴化四唑(MTT)、二氯二氢荧光素(DCFH-DA)、4',6-二氨基-2-苯基吲哚(DAPI)、吖啶橙/溴化乙啶(AO/EB)和western blot检测UMB的细胞毒性、细胞内活性氧(ROS)、细胞粘附蛋白和细胞凋亡作用。结果:UMB可抑制GBM细胞增殖和细胞粘附蛋白,并通过提高细胞ROS增加细胞凋亡。Bcl-2和Bcl-XL家族蛋白水平降低;相反,促凋亡蛋白Bad和Bim在UMB作用下呈数量依赖性升高。此外,经mb处理的GBM细胞抑制了N-cadherin、β-catenin、Slug和基质金属蛋白酶2 (MMP-2)的表达,而TIMP蛋白和E-cadherin水平则有所提高。结论:UMB具有抑制GBM细胞增殖转移和促进细胞凋亡的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advances in Clinical and Experimental Medicine
Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.70
自引率
4.80%
发文量
153
审稿时长
6-12 weeks
期刊介绍: Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.
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