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Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells
Here we demonstrated that sulforaphane-cysteine (SFN-Cys) regulated cell cycle-related protein expressions in G0/G1 and G2/M phases of U87MG cells via High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (HPLC-MS/MS) and proteomics analysis. Further, mRNA products of CDK4, CDK6...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521484/ https://www.ncbi.nlm.nih.gov/pubmed/32860670 http://dx.doi.org/10.18632/aging.103537 |
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author | Li, Juntao Zhou, Yan Yan, Yuting Zheng, Zhongnan Hu, Yabin Wu, Wei |
author_facet | Li, Juntao Zhou, Yan Yan, Yuting Zheng, Zhongnan Hu, Yabin Wu, Wei |
author_sort | Li, Juntao |
collection | PubMed |
description | Here we demonstrated that sulforaphane-cysteine (SFN-Cys) regulated cell cycle-related protein expressions in G0/G1 and G2/M phases of U87MG cells via High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (HPLC-MS/MS) and proteomics analysis. Further, mRNA products of CDK4, CDK6 and α-tubulin were significantly higher in glioblastoma than those in normal tissues, and these results were significantly correlated to pathological grades and clinical prognosis via analyzing TCGA and CGGA databases. Furthermore, Western blot showed that SFN-Cys downregulated CDK4, CDK6 and p-Rb in a dose-dependent manner and these results were reversed by p-ERK1/2 blocker PD98059 in U87MG and U373MG cells. The reductions of CDK4, CDK6 and p-Rb were reversed by proteasome inhibitor MG132; similarly, the upregulation of 26S proteasome by SFN-Cys was reversed by PD98059. Interestingly, SFN-Cys decreased CDK4 and CDK6 by phosphorylated ERK1/2-caused proteasomal degradation resulting in decreased Rb phosphorylation contributing to cell cycle arrest in G0/G1 phase. Besides, Western blot showed that SFN-Cys downregulated α-tubulin resulting in microtubule disruption and aggregation, and cell cycle arrest in G2/M phase and apoptosis. These results might help us understand the molecular etiology of glioblastoma progression to establish brand-new anti-cancer therapies. |
format | Online Article Text |
id | pubmed-7521484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-75214842020-10-02 Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells Li, Juntao Zhou, Yan Yan, Yuting Zheng, Zhongnan Hu, Yabin Wu, Wei Aging (Albany NY) Research Paper Here we demonstrated that sulforaphane-cysteine (SFN-Cys) regulated cell cycle-related protein expressions in G0/G1 and G2/M phases of U87MG cells via High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (HPLC-MS/MS) and proteomics analysis. Further, mRNA products of CDK4, CDK6 and α-tubulin were significantly higher in glioblastoma than those in normal tissues, and these results were significantly correlated to pathological grades and clinical prognosis via analyzing TCGA and CGGA databases. Furthermore, Western blot showed that SFN-Cys downregulated CDK4, CDK6 and p-Rb in a dose-dependent manner and these results were reversed by p-ERK1/2 blocker PD98059 in U87MG and U373MG cells. The reductions of CDK4, CDK6 and p-Rb were reversed by proteasome inhibitor MG132; similarly, the upregulation of 26S proteasome by SFN-Cys was reversed by PD98059. Interestingly, SFN-Cys decreased CDK4 and CDK6 by phosphorylated ERK1/2-caused proteasomal degradation resulting in decreased Rb phosphorylation contributing to cell cycle arrest in G0/G1 phase. Besides, Western blot showed that SFN-Cys downregulated α-tubulin resulting in microtubule disruption and aggregation, and cell cycle arrest in G2/M phase and apoptosis. These results might help us understand the molecular etiology of glioblastoma progression to establish brand-new anti-cancer therapies. Impact Journals 2020-08-29 /pmc/articles/PMC7521484/ /pubmed/32860670 http://dx.doi.org/10.18632/aging.103537 Text en Copyright: © 2020 Li et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Li, Juntao Zhou, Yan Yan, Yuting Zheng, Zhongnan Hu, Yabin Wu, Wei Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells |
title | Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells |
title_full | Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells |
title_fullStr | Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells |
title_full_unstemmed | Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells |
title_short | Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells |
title_sort | sulforaphane-cysteine downregulates cdk4 /cdk6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521484/ https://www.ncbi.nlm.nih.gov/pubmed/32860670 http://dx.doi.org/10.18632/aging.103537 |
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