Phenethyl isothiocyanate inhibits migration and invasion of human gastric cancer AGS cells through suppressing MAPK and NF-kappaB signal pathways.
Cell motility involves metastasis suppressors and other regulators that play an important role in tumor invasion and metastasis. Phenethyl isothiocyanate (PEITC), found in dietary cruciferous vegetables, has been found to exhibit antitumor properties and therefore is of special interest for the development of chemopreventive and chemotherapeutic agent for human cancers. Here, we report that in addition to its function as an anticancer agent, and PEITC can inhibit migration and invasion through the extracellular signal-regulated kinases 1/2 (ERK1/2), protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) signaling pathways in human gastric cells. The results from wound healing and Boyden chamber assays (migration and invasion) assay indicated that PEITC exhibited an inhibitory effect on the migration and invasion of AGS cells. Results from Western blotting examination demonstrated that PEITC exerted an inhibitory effect on the ERK1/2, mitogen-activated protein kinase kinase 7 (MKK7), MAP kinase kinase kinase 3 (MEKK3), son of sevenless 1 (SOS1), PKC, Ras homolog gene family, member A (Rho A) and urokinase-type plasminogen activator (uPA), causing the inhibition of matrix metallopeptidase-2 (MMP-2) and -9 then followed by the inhibition of invasion and migration of GAS cells in vitro. PEITC also inhibited Ras, growth factor receptor-bound protein 2 (GRB2), vascular endothelial growth factor (VEGF), focal adhesion kinase (FAK), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), causing inhibition of cell proliferation of AGS cells. Results from real-time PCR showed that PEITC inhibited the gene expressions of MMP-2, -7 and -9, FAK and RhoA after PEITC treatment for 24 and 48 h of AGS cells. Taken together, these findings may provide insight into a new mechanisms and functions of PEITC in migration and invasion of human gastric cancer AGS cells. Our data imply that molecular targeting of PKC leading to the inhibition of MMP-2 and -9 might be a useful strategy for the inhibition of migration and invasion of human gastric cancer.
Yang
Mei-Due
MD
Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan, ROC.
Lai
Kuang-Chi
KC
Lai
Tung-Yuan
TY
Hsu
Shu-Chun
SC
Kuo
Chao-Lin
CL
Yu
Chun-Shu
CS
Lin
Meng-Liang
ML
Yang
Jai-Sing
JS
Kuo
Hsiu-Maan
HM
Wu
Shin-Hwar
SH
Chung
Jing-Gung
JG
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009361:Neoplasm Invasiveness; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; C058305:phenethyl isothiocyanate; D011493:Protein Kinase C