Inhibition of Wnt/-Catenin Pathway by Dehydrocostus Lactone and Costunolide in Colon Cancer Cells

Abstract

Abnormal activation of -catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated -catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti-colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of -catenin. They also suppressed the nuclear translocation of galectin-3 that is one of the coactivators of -catenin in SW-480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW-480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti-colorectal cancer activities through inhibiting Wnt/-catenin pathway. Copyright (c) 2015 John Wiley & Sons, Ltd.