Involvement of matrix metalloproteinases in the inhibition of cell invasion and migration through the inhibition of NF-[kappa]B by the new synthesized ethyl 2-[N-p-chlorobenzyl-(2'-methyl)]anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOTO1007) in human cervical cancer Ca ski cells.
JOTO1007 (ethyl 2-[N-p-chlorobenzyl-(2'-methyl)] anilino-4-oxo-4,5-dihydrofuran -3-carboxylate) has anticancer effects in human cervical cancer Ca Ski cells. However, its mechanism of action on the cell migration and invasion of human cervical cancer Ca Ski cells is not fully understood. In this study, firstly, the effects of JOTO1007 on the migration and invasion of Ca Ski cells were examined by using matrigel counting. The results showed that JOTO1007 suppressed the migration and invasion of the Ca Ski cells. Secondly, the effect of JOTO1007 on the levels of proteins associated with cell metastasis was examined using Western blotting. The results indicated that JOTO1007 inhibited the levels of son of sevenless homolog 1 (SOS-1), growth factor receptor-bound protein 2 (GRB2), Ras homolog gene family, member A (RhoA), Rho-associated, coiled-coil containing protein kinase 1 (ROCK-1), focal adhesion kinase (FAK), phosphorylated-c-jun (p-c-jun), nuclear factor kappa B (NF-kappaB) p65, cyclooxygenase-2 (COX-2), extracellular signal-regulated kinases 1/2 (ERK1/2), matrix metalloproteinase-2 (MMP-2), MMP-7 and MMP-9 but promoted the levels of protein kinase C (PKC), phosphoinositide 3-kinases (PI3K), MAP kinase kinase kinase 3 (MEKK3), mitogen-activated protein kinase kinase 7 (MKK7), c-jun and inducible nitric oxide synthases (iNOS), while not affecting Ras, phosphorylated-ERK (p-ERK), p38 and c-jun N-terminal kinase 1/2 (JNK1/2), which finally led to the inhibition of migration and invasion of the Ca Ski cells in vitro. Overall, JOTO1007 inhibited NF-kappaB which then led to the inhibition of the MMP-2, -7 and -9 expression followed by the inhibition of migration and invasion in the Ca Ski cells.
Huang
An-Cheng
AC
Department of Nursing, St. Mary's Medicine Nursing and Management College, Sansing Township, Yilan County 266, Taiwan, R.O.C.
Hsu
Shu-Chun
SC
Kuo
Chao-Lin
CL
Liao
Ching-Lung
CL
Lai
Kuang-Chi
KC
Lin
Tsung-Ping
TP
Wu
Shin-Hwar
SH
Lu
Hsu-Feng
HF
Tang
Nou-Ying
NY
Yang
Jai-Sing
JS
Chung
Jing-Gung
JG
D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020837:SOS1 Protein / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D002264:Carboxylic Acids; D005663:Furans; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D016328:NF-kappa B; D020837:SOS1 Protein; C521182:ethyl-2-(N-p-chlorobenzyl-(2'-methyl))anilino-4-oxo-4,5-dihydrofuran-3-carboxylate; D020782:Matrix Metalloproteinases