Diarylheptanoids from lesser galangal suppress human colon cancer cell growth through modulating Wnt/β-catenin pathway

The Wnt/β-catenin pathway plays a central role in cell growth and differentiation but abnormal activation causes colorectal carcinogenesis. 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 food materials, 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/T-cell 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 diarylheptanoid from lesser galangal exerts anti-colon 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.