Jae-Ha Ryu
Sookmyung Womens University, Korea
Title: Plant derived diarylheptanoids as Wnt/β-catenin pathway inhibitors
Biography
Biography: Jae-Ha Ryu
Abstract
The Wnt/β-catenin signaling pathway plays a primary role in the differentiation, proliferation, and function of many cells but disruption of the pathway is involved in cancer development including colon cancer. Colorectal cancer is the third most common cancer in males and the second most common cancer in females, accounting for approximately 10% of all cancer-related deaths. Inhibiting the Wnt/β-catenin pathway can be a good strategy for chemoprevention and treatment of colorectal cancer. While screening for Wnt/β-catenin pathway inhibitors from medicinal plants, we found that (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (compound 1), among six diarylheptanoids from lesser galangal (Alpinia officinarum), most potently suppressed Wnt3a-induced β-catenin/Tcell factor activity. Moreover, compound 1 suppressed proliferation of colon cancer cells by inhibiting β-catenin translocation to the nucleus by disrupting the β-catenin/galectin-3 complex. Furthermore, a structure–activity realtionship study implicated that the enone group in the linker is critical and the hydroxy substituent on the aromatic ring is generally preferred for activity. Our findings suggest that diarylheptanoids from lesser galangal exerts anticolon cancer activity by down regulating the Wnt/β-catenin pathway. Bioactive diarylheptanoids and the basic understanding of their structure–activity relationship could be utilized to develop potential candidates for β-catenin-targeted cancer treatment.
