title: Phenethyl isothiocyanate suppresses EGF-stimulated SAS human oral squamous carcinoma cell invasion by targeting EGF receptor signaling.
abstract: Phenethyl isothiocyanate (PEITC) is a natural compound that is involved in chemoprevention as well as inhibition of cell growth and induction of apoptosis in several types of cancer cells. Previous studies have revealed that PEITC suppresses the invasion of AGS gastric and HT-29 colorectal cancer cells. However, the effects of PEITC on the metastasis of SAS oral cancer cells remain to be determined. Our results showed that PEITC treatment inhibited the invasion of EGF-stimulated SAS cells in a concentration-dependent manner, but appeared not to affect the cell viability. The expression and enzymatic activities of matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) were suppressed by PEITC. Concomitantly, we observed an increase in the protein expression of both tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 (TIMP-2) in treated cells. Furthermore, PEITC treatments decreased the protein phosphorylation of epidermal growth factor receptor (EGFR) and downstream signaling proteins including PDK1, PI3K (p85), AKT, phosphorylated IKK and IκB to inactivate NF-κB for the suppression of MMP-2 and MMP-9 expression. In addition, PEITC can trigger the MAPK signaling pathway through the increase in phosphorylated p38, JNK and ERK in treated cells. Our data indicate that PEITC is able to inhibit the invasion of EGF-stimulated SAS oral cancer cells by targeting EGFR and its downstream signaling molecules and finally lead to the reduced expression and enzymatic activities of both MMP-2 and MMP-9. These results suggest that PEITC is promising for the therapy of oral cancer metastasis.
authors.affiliation: Graduate Institute of Molecular Systems Biomedicine, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Hui-Jye
authors.initials: HJ
authors.lastname: Chen
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Lin
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Lee
authors.forename: Nai-Chen
authors.initials: NC
authors.lastname: Shih
authors.forename: Sakae
authors.initials: S
authors.lastname: Amagaya
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Lin
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
chemical_list: D016588:Anticarcinogenic Agents; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051550:I-kappa B Kinase; D017879:Isothiocyanates; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C000631429:PDK1 protein, human; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; C058305:phenethyl isothiocyanate; C522361:MMP2 protein, human; C579270:MMP9 protein, human