Quercetin is a promising chemopreventive agent against
cancer that inhibits
tumor progression by inducing cell cycle arrest and promoting apoptotic cell death. Recently, the Wnt/β-
catenin signaling pathway has been implicated in mammary
tumorigenesis, where its abnormal activation is associated with the development of
breast cancer. Thus, the objective of this study was to examine the
biological activities of
quercetin against
mammary cancer cells, and to determine whether
quercetin could regulate the Wnt/β-
catenin signaling pathway.
Quercetin showed dose-dependent inhibition of cell growth and induced apoptosis in 4T1 cells. Treatment of 20 µM
quercetin suppressed ~50% of basal TopFlash
luciferase activity. Moreover, the inhibitory effect of
quercetin on the Wnt/β-
catenin signaling pathway was confirmed by the reduced stabilization of the β-
catenin protein. Among various antagonists screened for the Wnt/β-
catenin signaling pathway, the expression of DKK1, 2 and 3 was induced
after treatment with 20 µM of
quercetin. Stimulation with recombinant DKK1
protein, showed suppressive cell growth of
mammary cancer cells instead of
quercetin. When 4T1 cells were treated with recombinant Wnt3a or LiCl along with
quercetin, both stimulators for the Wnt/β-
catenin signaling pathway were able to restore the suppressed cell viability by
quercetin. Thus, our data suggest that
quercetin exerts its anticancer activity through the downregulation of Wnt/β-
catenin signaling activity. These results indicate for the first time that
quercetin decreases cell viability and induces apoptosis in murine
mammary cancer cells, which is possibly mediated by DKK-dependent inhibition of the Wnt/β-
catenin signaling pathway. In conclusion, our findings suggest that
quercetin has great potential value as chemotherapeutic agent for
cancer treatment, especially in
breast cancer controlled by Wnt/β-
catenin signaling activity.