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KMID : 1234420120400010050
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Korean Journal of Microbiololgy and Biotechnology
2012 Volume.40 No. 1 p.50 ~ p.56
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Silybin Synergizes with Wnt3a in Activation of the Wnt/β-catenin Signaling Pathway through Stabilization of Intracellular β-Catenin Protein
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Kim Taeyeoun
Oh Sang-Taek
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Abstract
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The Wnt/β-catenin signaling pathway regulates diverse developmental processes and adult tissue homeostasis. Inappropriate regulation of this pathway has been associated with human diseases, such as cancers, osteoporosis, and Alzheimer’s disease. Using a cell-based chemical screening with natural compounds, we discovered silybin, a plant flavonoid isolated from the Silybum marianum, which activated the Wnt/β-catenin signaling pathway in a synergy with Wnt3a-conditioned medium (Wnt3a-CM). In the presence of Wnt3a-CM, silybin up-regulated β-catenin response transcription (CRT) in HEK293-FL reporter cells and 3T3-L1 preadipocytes through stabilization of intracellular β-catenin protein. Silybin and Wnt3a-CM synergistically reduced expression of important adipocyte marker genes including peroxisome-proliferator-activated receptorγ (PPARγ) and CAATT enhancer-binding protein α (C/EBPα) in 3T3-L1 preadipocytes, accompanied by the activation of Wnt/β-catenin signaling pathway. Taken together, our findings indicate that silybin is a small-molecule synergist of the Wnt/β-catenin signaling pathway and can be used as a controllable reagent for investigating biological processes that involve the Wnt/β-catenin signaling pathway.
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KEYWORD
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Wnt/b-catenin pathway, silybin, synergist
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