Research Paper Volume 12, Issue 17 pp 16837—16851

Sulforaphane-cysteine downregulates CDK4 /CDK6 and inhibits tubulin polymerization contributing to cell cycle arrest and apoptosis in human glioblastoma cells

Juntao Li1,2, , Yan Zhou1,2, , Yuting Yan1,2, , Zhongnan Zheng1,2, , Yabin Hu1,2, , Wei Wu1,2, ,

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
  • 2 Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University, Beijing, China

Received: December 3, 2019       Accepted: April 27, 2020       Published: August 29, 2020
How to Cite

Copyright: © 2020 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


GBM: glioblastoma; SFN-Cys: sulforaphane-cysteine; CDK4: cyclin-dependent kinase 4; CDK6: cyclin-dependent kinase 6; Rb: retinoblastoma.