Antimetastatic potentials of flavones on oral cancer cell via an inhibition of matrix-degrading proteases.
OBJECTIVE
Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers with a poor prognosis due to frequent lymph node metastasis and local invasion. A growing number of in vitro studies have been conducted on the potential anticancer activity of flavonoids in various cancer cell lines. However, the antimetastatic activities of flavones, one subclass of flavonoids, in human oral squamous carcinoma SCC-4 cells have not been understood clearly.


METHODS
The present study investigated the effect of four flavones on invasion and migration of SCC-4 cells to find that 7-hydroxyflavanone, 5,6,7-trihydroxyflavanone, and 4',5,7-trihydroxyflavanone exerted a dose-dependent inhibitory effect on the invasion and migration of SCC-4 cells.


RESULTS
Results from zymography and Western blot showed that flavones treatment may decrease the expressions of matrix metalloproteinase (MMP)-2, urokinase plasminogen activator (u-PA) in a concentration-dependent manner, together with altered expression levels of their endogenous inhibitors, which are tissue inhibitor of metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, an in vivo chorioallantoic membrane (CAM) intravasation assay was also treated and analysed to reveal the antimetastatic effect.


CONCLUSIONS
Our data suggest that 7-hydroxyflavanone, 5,6,7-trihydroxyflavanone, and 4',5,7-trihydroxyflavanone could be applicable to be a potential antimetastatic agent of SCC-4 cells.
Yang
Shun-Fa
SF
Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Yang
Wen-En
WE
Kuo
Wu-Hsien
WH
Chang
Horng-Rong
HR
Chu
Shu-Chen
SC
Hsieh
Yih-Shou
YS
D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D044950:Flavanones / Q000627:therapeutic use; D047309:Flavones / Q000627:therapeutic use*; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D014062:Tongue Neoplasms / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
C107364:5,6,7-trimethoxyflavone; D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D047309:Flavones; D005419:Flavonoids; D017395:Plasminogen Activator Inhibitor 1; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C005273:naringenin; C429845:7-hydroxyflavone