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白藜芦醇通过激活锌指蛋白Tristetraprolin诱导胶质瘤细胞凋亡。

Resveratrol Induces Glioma Cell Apoptosis through Activation of Tristetraprolin.

作者信息

Ryu Jinhyun, Yoon Nal Ae, Seong Hyemin, Jeong Joo Yeon, Kang Seokmin, Park Nammi, Choi Jungil, Lee Dong Hoon, Roh Gu Seob, Kim Hyun Joon, Cho Gyeong Jae, Choi Wan Sung, Park Jae-Yong, Park Jeong Woo, Kang Sang Soo

机构信息

Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.

Department of Physiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.

出版信息

Mol Cells. 2015 Nov;38(11):991-7. doi: 10.14348/molcells.2015.0197. Epub 2015 Nov 4.

DOI:10.14348/molcells.2015.0197
PMID:26537190
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4673414/
Abstract

Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of AREs-containing mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4'-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetraprolin (TTP). Res increased TTP expression in U87MG human glioma cells. Res-induced TTP destabilized the urokinase plasminogen activator and urokinase plasminogen activator receptor mRNAs by binding to the ARE regions containing the 3' untranslated regions of their mRNAs. Furthermore, TTP induced by Res suppressed cell growth and induced apoptosis in the human glioma cells. Because of its regulation of TTP expression, these findings suggest that the bioactive dietary compound Res can be used as a novel anti-cancer agent for the treatment of human malignant gliomas.

摘要

锌指蛋白36（TTP）是一种富含AU元件（AREs）的结合蛋白，它可调节含AREs的mRNA的降解，如原癌基因、抗凋亡基因和免疫调节基因。尽管TTP在多种人类癌症中表达较低，但TTP表达受抑制的机制尚未完全明确。在此，我们证明白藜芦醇（3,5,4'-三羟基茋，Res），一种天然存在的化合物，通过激活锌指蛋白36（TTP）诱导胶质瘤细胞凋亡。Res增加了U87MG人胶质瘤细胞中TTP的表达。Res诱导的TTP通过与包含其mRNA 3'非翻译区的ARE区域结合，使尿激酶型纤溶酶原激活剂和尿激酶型纤溶酶原激活剂受体mRNA不稳定。此外，Res诱导的TTP抑制人胶质瘤细胞的生长并诱导其凋亡。由于其对TTP表达的调节作用，这些发现表明生物活性膳食化合物Res可作为一种新型抗癌剂用于治疗人类恶性胶质瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/cf12d19e6620/molce-38-11-991f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/3a2282ca6c77/molce-38-11-991f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/8956de87f6e3/molce-38-11-991f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/a44762382fb7/molce-38-11-991f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/129c3cc54313/molce-38-11-991f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/076e42e52367/molce-38-11-991f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/cf12d19e6620/molce-38-11-991f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/3a2282ca6c77/molce-38-11-991f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/8956de87f6e3/molce-38-11-991f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/a44762382fb7/molce-38-11-991f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/129c3cc54313/molce-38-11-991f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/076e42e52367/molce-38-11-991f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd3f/4673414/cf12d19e6620/molce-38-11-991f6.jpg

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