title: Allyl isothiocyanate inhibits cell metastasis through suppression of the MAPK pathways in epidermal growth factor‑stimulated HT29 human colorectal adenocarcinoma cells.
abstract: Allyl isothiocyanate (AITC) has been found to present sources from consumed cruciferous vegetables. AITC is known to possess pharmacological and anticancer activities. The present study was designed to test the hypothesis that AITC suppressed the invasion and migration of epidermal growth factor (EGF)-stimulated HT29 cells and to elucidate the mechanisms for the antimetastatic abilities in vitro. The invasion and migration of EGF-stimulated HT29 cells were determined individually by Transwell cell invasion and wound-healing assays. Our results showed that AITC effectively inhibited both the invasive and migratory ability of HT29 cells. Furthermore, AITC downregulated the protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and mitogen-activated protein kinases (MAPKs) (p-JNK, p-ERK and p-p38) by western blot analysis in HT29 cells following EGF induction. Thus, the metastatic responses in AITC-treated HT29 cells after EGF stimulation were mediated by the MMP-2/-9 and MAPK signaling pathways. We also used gene expression microarrays to investigate the gene levels related to cell growth, G-protein coupled receptor, angiogenesis, cell adhesion, cell cycle and mitosis, cell migration, cytoskeleton organization, DNA damage and repair, transcription and translation, EGFR and PKB/mTOR signals. In summary, it is possible that AITC suppresses the invasion and migration of EGF-induced HT29 cells, resulting from MMP-2/-9 and MAPKs. Hence, AITC may be beneficial in the treatment of human colorectal adenocarcinoma in the future.
authors.affiliation: School of Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
authors.forename: Kuang-Chi
authors.initials: KC
authors.lastname: Lai
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Yih-Jing
authors.initials: YJ
authors.lastname: Tang
authors.forename: Jo-Hua
authors.initials: JH
authors.lastname: Chiang
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Chen
authors.forename: I-Li
authors.initials: IL
authors.lastname: Chen
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005520:Food Preservatives / Q000494:pharmacology*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D005520:Food Preservatives; D017879:Isothiocyanates; D004815:Epidermal Growth Factor; C004471:allyl isothiocyanate; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9