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氧化白藜芦醇调节MCF-7细胞中与细胞凋亡、细胞周期调控和DNA修复相关的基因。

Oxyresveratrol Modulates Genes Associated with Apoptosis, Cell Cycle Control and DNA Repair in MCF-7 Cells.

作者信息

Radapong Sarayut, Chan Kelvin, Sarker Satyajit D, Ritchie Kenneth J

机构信息

Toxicology Laboratory, Medicinal Plant Research Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom.

出版信息

Front Pharmacol. 2021 Jul 1;12:694562. doi: 10.3389/fphar.2021.694562. eCollection 2021.

Abstract

Oxyresveratrol (OXY) is a small molecule phytochemical which has been reported to have important biological function. The aim of this study was to elucidate the gene expression and biological pathways altered in MCF-7, breast cancer cells following exposure to OXY. The cytotoxicity to different cancer cell lines was screened using MTT assay and then whole gene expression was elucidated using microarray. The pathways selected were also validated by quantitative PCR analysis, fluorometric and western blot assay. A total of 686 genes were found to have altered mRNA expression levels of two-fold or more in the 50 μM OXY-treated group, while 2,338 genes were differentially expressed in the 100 µM-treated group. The relevant visualized global expression patterns of genes and pathways were generated. Apoptosis was activated through mitochondria-lost membrane potential, caspase-3 expression and chromatin condensation without DNA damage. G0/G1 and S phases of the cell cycle control were inhibited dose-dependently by the compound. Rad51 gene (DNA repair pathway) was significantly down-regulated ( < 0.0001). These results indicate that OXY moderates key genes and pathways in MCF-7 cells and that it could be developed as a chemotherapy or chemo-sensitizing agent.

摘要

氧化白藜芦醇(OXY)是一种小分子植物化学物质,据报道具有重要的生物学功能。本研究的目的是阐明MCF-7乳腺癌细胞在暴露于OXY后基因表达和生物途径的变化。使用MTT法筛选对不同癌细胞系的细胞毒性,然后使用微阵列阐明全基因表达。所选途径也通过定量PCR分析、荧光分析和蛋白质印迹法进行验证。在50μM OXY处理组中,共发现686个基因的mRNA表达水平变化了两倍或更多,而在100μM处理组中有2338个基因差异表达。生成了相关的基因和途径可视化全局表达模式。通过线粒体膜电位丧失、半胱天冬酶-3表达和染色质凝聚激活凋亡,且无DNA损伤。该化合物剂量依赖性地抑制细胞周期控制的G0/G1期和S期。Rad51基因(DNA修复途径)显著下调(<0.0001)。这些结果表明,OXY调节MCF-7细胞中的关键基因和途径,并且它可以被开发为化疗或化疗增敏剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/395a/8294160/4b6afb92e7f7/fphar-12-694562-g001.jpg

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