title: Inhibition of invasion and migration by newly synthesized quinazolinone MJ-29 in human oral cancer CAL 27 cells through suppression of MMP-2/9 expression and combined down-regulation of MAPK and AKT signaling.
abstract: Anti-metastasis by reducing cellular migration and invasion and by deregulating the expression of matrix metalloproteinases (MMPs) is a therapeutic approach for cancer treatment. The objective of this study focused on the effects of the novel compound 6-pyrrolidinyl-2-(2-hydroxyphenyl)-4-quinazolinone (MJ-29) regarding anti-metastatic actions on human oral squamous cell carcinoma CAL 27 cells and on the verification of the underlying related molecular mechanisms of this event. MJ-29 concentration- and time-dependently caused a suppression of cell adhesive ability utilizing cell adhesion assay; it also inhibited the migration and invasion of CAL 27 cells using scratch wound closure and transwell invasion assays in a concentration-dependent response. Importantly, we confirmed that the applied concentration range of MJ-29 exhibited no dramatic influence of cytotoxicity on CAL 27 cells using the thiazolyl blue tetrazolium bromide assay. MJ-29 also attenuated the enzymatic activity of MMP-2 and MMP-9. Furthermore, we found that activation of their upstream protein kinases, by MJ-29, potentially exerted an inhibitory effect on the phosphorylated protein levels of extracellular regulated protein kinase 1/2, p38 and c-Jun N-terminal kinase 1/2, as well as serine/threonine kinase AKT by MJ-29 in CAL 27 cells. The expression of RAS and focal adhesion kinase was also down-regulated in MJ-29-treated CAL 27 cells. Collectively, these findings provide further evidence for the molecular signaling basis of the effects of MJ-29 on suppression of migration and invasion which might be useful as a therapeutic strategy to treat human oral cancer.
authors: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, ROC.
authors: Chi-Cheng
authors: CC
authors: Lu
authors: Jai-Sing
authors: JS
authors: Yang
authors: Jo-Hua
authors: JH
authors: Chiang
authors: Mann-Jen
authors: MJ
authors: Hour
authors: Sakae
authors: S
authors: Amagaya
authors: Kung-Wen
authors: KW
authors: Lu
authors: Jing-Pin
authors: JP
authors: Lin
authors: Nou-Ying
authors: NY
authors: Tang
authors: Tsung-Han
authors: TH
authors: Lee
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C575388:6-pyrrolidinyl-2-(2-hydroxyphenyl)-4-quinazolinone; D061965:Matrix Metalloproteinase Inhibitors; D011759:Pyrrolidines; D052999:Quinazolinones; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9