Benzyl isothiocyanate (BITC) inhibits migration and invasion of human gastric cancer AGS cells via suppressing ERK signal pathways.
Metastasis suppressors and associated other regulators of cell motility play a critical initial role in tumor invasion and metastases. Benzyl isothiocyanate (BITC) is a hydrolysis compound of glucotropaeolin in dietary cruciferous vegetables. BITC has been found to exhibit prevention of cancers in laboratory animals and might also be chemoprotective in humans. Here, the purpose of this study was to investigate the effects of BITC on cell proliferation, migration, invasion and mitogen-activated protein kinase (MAPK) pathways of AGS human gastric cancer cells. Wound healing and Boyden chamber (migration and invasion) assays demonstrated that BITC exhibited an inhibitory effect on the abilities of migration and invasion in AGS cancer cells. BITC suppressed cell migration and invasion of AGS cells in a dose-dependent manner. Results from Western blotting indicated that BITC exerted an inhibitory effect on the ERK1/2, Ras, GRB2, Rho A, iNOS, COX-2 for causing the inhibitions of MMP-2, -7 and -9 then followed by the inhibitions of invasion and migration of AGS cells in vitro. BITC also promoted MKK7, MEKK3, c-jun, JNK1/2, VEGF, Sos1, phosphoinositide 3-kinase (PI3K), PKC, nuclear factor-kappaB (NF-κB) p65 in AGS cells. Results from real-time polymerized chain reaction (PCR) showed that BITC inhibited the gene expressions of MMP-2,-7 -9, FAK, ROCK1 and RhoA after BITC treatment for 24 and 48 hours in AGS cells. Taken together, the finding may provide new mechanisms and functions of BITC, which inhibit migration and invasion of human gastric cancer AGS cells.
Ho
Chin-Chin
CC
Department of Nursing, Central Taiwan University of Science and Technology, Taichung, Taiwan.
Lai
Kuang-Chi
KC
Hsu
Shu-Chun
SC
Kuo
Chao-Lin
CL
Ma
Chia-Yu
CY
Lin
Meng-Liang
ML
Yang
Jai-Sing
JS
Chung
Jing-Gung
JG
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D017879:Isothiocyanates; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
D017879:Isothiocyanates; D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; C031403:benzyl isothiocyanate; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9