JOURNAL ARTICLE

Silibinin inhibits Wnt/β-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells

Wenyan Lu, Cuihong Lin, Taj D King, Honghong Chen, Robert C Reynolds, Yonghe Li
Cellular Signalling 2012, 24 (12): 2291-6
22820499
Silibinin is a natural compound isolated from milk thistle seed extracts, and has traditionally been used as a hepatoprotectant. A number of studies have also established the cancer therapeutic and chemopreventive role of silibinin in both in vitro and in vivo models. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for the Wnt/β-catenin pathway and represents a promising target for cancer prevention and therapy. In the present study, we found that silibinin was able to repress endogenous LRP6 expression and block Wnt3A-induced LRP6 phosphorylation and Wnt/β-catenin signaling activation in HEK293 cells. Importantly, silibinin was also able to suppress endogenous LRP6 expression and phosphorylation and block Wnt/β-catenin signaling in prostate cancer PC-3 and DU-145 cells and breast cancer MDA-MB-231 and T-47D cells. Mechanistically, silibinin inhibited LRP6 promoter activity and decreased LRP6 mRNA levels in prostate and breast cancer cells. Finally, we demonstrated that silibinin displayed anticancer activity with IC(50) values comparable to those shown to suppress LRP6 expression and Wnt/β-catenin signaling activities in prostate and breast cancer cells. Our data indicate that silibinin is a novel small molecule Wnt/β-catenin signaling inhibitor by suppressing Wnt co-receptor LRP6 expression at the transcription level, and that the anti-cancer activity of silibinin is associated with its inhibitory effect on Wnt/LRP6 signaling.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
22820499
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"