PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression

Chou,Yu-Cheng; Chang,Meng-Ya; Wang,Mei-Jen; Yu,Fu-Shun; Liu,Hsin-Chung; Harnod,Tomor; Hung,Chih-Huang; Lee,Hsu-Tung; Chung,Jing-Gung

doi:10.3892/or.2015.4260

PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression

Authors:
- Yu-Cheng Chou
- Meng-Ya Chang
- Mei-Jen Wang
- Fu-Shun Yu
- Hsin-Chung Liu
- Tomor Harnod
- Chih-Huang Hung
- Hsu-Tung Lee
- Jing-Gung Chung
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Affiliations: Division of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung 407, Taiwan, R.O.C., Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, R.O.C., School of Dentistry, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Neurosurgery, Buddhist Tzu Chi General Hospital and College of Medicine, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
Published online on: September 8, 2015 https://doi.org/10.3892/or.2015.4260
Pages: 2489-2496

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Abstract

Glioblastoma is the most aggressive primary brain malignancy, and the efficacy of multimodality treatments remains unsatisfactory. Phenethyl isothiocyanate (PEITC), one member of the isothiocyanate family, was found to inhibit the migration and invasion of many types of human cancer cells. In our previous study, PEITC induced the apoptosis of human brain glioblastoma GBM 8401 cells through the extrinsic and intrinsic signaling pathways. In the present study, we first investigated the effects of PEITC on the migration and invasion of GBM 8401 cells. PEITC decreased the migration of GBM 8401 cells in a dose-dependent manner as determined from scratch wound healing and Transwell migration assays. The percentage of inhibition ranged from 46.89 to 15.75%, and from 27.80 to 7.31% after a 48-h treatment of PEITC as determined from the Transwell migration assay and invasion assay, respectively. The western blot analysis indicated that PEITC decreased the levels of proteins associated with migration and invasion, Ras, uPA, RhoA, GRB2, p-p38, p-JNK, p-ERK, p65, SOS1, MMP-2, MMP-9 and MMP-13, in a dose-dependent manner. Real-time PCR analyses revealed that PEITC reduced the mRNA levels of MMP-2, MMP-7, MMP-9 and RhoA in a dose- and time-dependent manner. PEITC exhibited potent anticancer activities through the inhibition of migration and invasion in the GBM 8401 cells. Our findings elucidate the possible molecular mechanisms and signaling pathways of the anti-metastatic effects of PEITC on human brain glioblastoma cells, and PEITC may be considered as a therapeutic agent.

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