Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids.
OBJECTIVE
Stromelysin 1 (matrix metalloproteinase 3; MMP-3) is an enzyme known to be involved in tumor invasion and metastasis. In this study, flavonoids from vegetables and fruits, such as quercetin, kaempferol, genistein, genistin, and daidzein, were tested for their ability to modulate the secretion and activity of MMP-3 in the MDA-MB-231 breast cancer cell line. In addition, we investigated the in vitro effects of flavonoids on MDA-MB-231 cell invasion.


METHODS
The toxic concentration range of flavonoids was evaluated using the MTT assay. The ability of MDA-MB-231 cells to invade was evaluated using a modified Boyden chamber system. The activity of MMP-3 was determined by casein zymography. The secretion of MMP-3 was evaluated using Western blotting, casein zymography and confirmed by ELISA.


RESULTS
Some putative flavonoids, ie, quercetin and kaempferol (flavonols), significantly inhibited the in vitro invasion of MDA-MB-231 cells in a concentration-dependent manner, with IC(50) values of 27 and 30 micromol/L, respectively. Quercetin and kaempferol also reduced MMP-3 activity in a dose-dependent manner, with IC(50) values in the range of 30 micromol/L and 45 micromol/L, respectively. None of the flavonoids had a significant effect on the secretion of MMP-3.


CONCLUSIONS
These data show that the flavonols quercetin and kaempferol have higher anti-invasion potency and higher MMP-3 inhibitory activity than isoflavones genistein, genistin and daidzein. In contrast, neither flavonols nor isoflavones have any effect on MMP-3 secretion.
Phromnoi
Kanokkarn
K
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Yodkeeree
Supachai
S
Anuchapreeda
Songyot
S
Limtrakul
Pornngarm
P
D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness / Q000517:prevention & control*
D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; D019278:Matrix Metalloproteinase 3