Abstract:
: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.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Li J,Zhou Y,Yan Y,Zheng Z,Hu Y,Wu Wdoi
10.18632/aging.103537subject
Has Abstractpub_date
2020-08-29 00:00:00pages
16837-16851issue
17issn
1945-4589pii
103537journal_volume
12pub_type
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