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.
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.
Division of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung 407, Taiwan, R.O.C.
Yu-Cheng
YC
Chou
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
Meng-Ya
MY
Chang
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
Mei-Jen
MJ
Wang
School of Dentistry, China Medical University, Taichung 404, Taiwan, R.O.C.
Fu-Shun
FS
Yu
Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
Hsin-Chung
HC
Liu
Department of Neurosurgery, Buddhist Tzu Chi General Hospital and College of Medicine, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
Tomor
T
Harnod
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
Chih-Huang
CH
Hung
Division of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung 407, Taiwan, R.O.C.
Hsu-Tung
HT
Lee
Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
Jing-Gung
JG
Chung
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004794:Enzyme Repression; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D017879:Isothiocyanates; C066737:RHOA protein, human; C058305:phenethyl isothiocyanate; D014568:Urokinase-Type Plasminogen Activator; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein