Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3).
BACKGROUND
Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of cancer death and may complicate the clinical management, even lead to death. Quercetin is a flavonoid and widely used as an antioxidant and recent studies have revealed its pleiotropic anticancer and antiproliferative capabilities. Gelatinases A and B (matrixmetalloproteinases 2 and 9) are enzymes known to involve in tumor invasion and metastases. In this study, we observed the precise involvement of quercetin role on these proteinases expression and activity.


METHODS
PC-3 cells were treated with quercetin at various concentrations (50 and 100 microM), for 24 h period and then subjected to western blot analysis to investigate the impact of quercetin on matrix metalloproteinase-2 (MMP-2) and 9 (MMP-9) expressions. Conditioned medium and cell lysate of quercetin-treated PC-3 cells were subjected to western blot analysis for proteins expression of MMP-2 and MMP-9. Gelatin zymography was also performed in quercetin treated PC-3 cells.


RESULTS
The results showed that quercetin treatment decreased the expressions of MMP-2 and MMP-9 in dose-dependent manner. The level of pro-MMP-9 was found to be high in the 100 microM quercetin-treated cell lysate of PC-3 cells, suggesting inhibitory role of quercetin on pro-MMP-9 activation. Gelatin zymography study also showed the decreased activities of MMP-2 and MMP-9 in quercetin treated cells.


CONCLUSIONS
Hence, we speculated that inhibition of metastasis-specific MMPs in cancer cells may be one of the targets for anticancer function of quercetin, and thus provides the molecular basis for the development of quercetin as a novel chemopreventive agent for metastatic prostate cancer.
Vijayababu
M R
MR
Department of Endocrinology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani campus, Chennai, 600 113, India.
Arunkumar
A
A
Kanagaraj
P
P
Venkataraman
P
P
Krishnamoorthy
G
G
Arunakaran
J
J
D015153:Blotting, Western; D045744:Cell Line, Tumor; D018890:Chemoprevention; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics*; D061965:Matrix Metalloproteinase Inhibitors; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D011794:Quercetin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9