Sulforaphane inhibits invasion via activating ERK1/2 signaling in human glioblastoma U87MG and U373MG cells

• Published in: PloS one Vol. 9; no. 2; p. e90520
• Main Authors: Li, Chunliu, Zhou, Yan, Peng, Xiaohui, Du, Lianlian, Tian, Hua, Yang, Gaoxiang, Niu, Jing, Wu, Wei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-02-2014; Public Library of Science (PLoS)
• Subjects: Activation; Anticarcinogenic Agents - pharmacology; Apoptosis; Assaying; Biochemistry; Biology; Blotting, Western; Brain cancer; Breast cancer; Cancer therapies; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Survival - drug effects; Chemical compounds; Chemotherapy; Cytokines; Development and progression; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Enzyme Activation - drug effects; Epidemiology; Extracellular signal-regulated kinase; Flavonoids - pharmacology; Gelatin; Gelatinase A; Glioblastoma; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastomas; Health aspects; Humans; Hyaluronan Receptors - metabolism; Inhibition; Isothiocyanates - pharmacology; Laboratories; MAP Kinase Signaling System - drug effects; Matrix metalloproteinase; Matrix Metalloproteinase 9 - metabolism; Medical prognosis; Medicine; Metalloproteinase; Metastasis; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Molecular biology; Molecular interactions; Neoplasm Invasiveness; Pharmacology; Phosphorylation - drug effects; Prognosis; Prostate cancer; Protein Kinase Inhibitors - pharmacology; Proteins; Pseudopodia; Public health; Radiation therapy; Signaling; Studies; Sulforaphane; Tumors; Up-Regulation - drug effects; Western blotting; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090520

Glioblastoma has highly invasive potential, which might result in poor prognosis and therapeutic failure. Hence, the key we study is to find effective therapies to repress migration and invasion. Sulforaphane (SFN) was demonstrated to inhibit cell growth in a variety of tumors. Here, we will further investigate whether SFN inhibits migration and invasion and find the possible mechanisms in human glioblastoma U87MG and U373MG cells.
First, the optimal time and dose of SFN for migration and invasion study were determined via cell viability and cell morphological assay. Further, scratch assay and transwell invasion assay were employed to investigate the effect of SFN on migration and invasion. Meanwhile, Western blots were used to detect the molecular linkage among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2 (MMP-2) and CD44v6. Furthermore, Gelatin zymography was performed to detect the inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 µM) was integrated to find the link between activated ERK1/2 and invasion, MMP-2 and CD44v6.
The results showed that SFN (20 µM) remarkably reduced the formation of cell pseudopodia, indicating that SFN might inhibit cell motility. As expected, scratch assay and transwell invasion assay showed that SFN inhibited glioblastoma cell migration and invasion. Western blot and Gelatin zymography showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to the downregulated MMP-2 expression and activity, and the upregulated CD44v6 expression. These molecular interactions resulted in the inhibition of cell invasion.
SFN inhibited migration and invasion processes. Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its activity and upregulated CD44v6. SFN might be a potential therapeutic agent by activating ERK1/2 signaling against human glioblastoma.