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

Abstract

Abnormal activation of β-catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β-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 β-catenin. They also suppressed the nuclear translocation of galectin-3 that is one of the coactivators of β-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/β-catenin pathway.

Wnt/catenin β1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer

“…Mucous epithelial cells require regular renewal and, therefore, intestinal tract stem/ancestral cells in the intestinal crypt regularly proliferate and differentiate (22). Following damage to, and the external stimulation of, mucous epithelial cells, stem/ancestral cells may proliferate and differentiate into numerous mucosal cells to maintain mucosal structural integrity (23). In the gathering areas of the stem/ancestral cells, in the bottom of the normal intestinal crypt, the gathering of CTNNB1 in the cell nucleus may be observed.…”

“…In multiple malignant tumors, including breast, gastric, thyroid, lung, prostate and skin cancer, the abnormal activation of the Wnt/CTNNB1 signaling pathway and of pathway-inhibiting proteins, including downregulated expression or inactivation of dickkopf like acrosomal protein, secreted frizzled-associated proteins or WNT inhibitory factor may be demonstrated, and has been studied in the occurrence and development of colorectal cancer (26). The abnormal activation of the Wnt/CTNNB1 signaling pathway not only represents an early event of colorectal cancer development, but is also important for its progression (23). The present study demonstrated that downregulating Wnt and CTNNB1 expression suppressed miR183 expression and CCND1 protein expression in HCT-116 cells.…”

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

“…These results reveal that compound 1 inhibits nuclear translocation of β-catenin and galectin-3 by blocking accumulation of the β-catenin/galectin-3 complex. We reported previously that sesquiterpenes and a chromene-derivative from medicinal plants reduce colon cancer cell proliferation by suppressing nuclear β-catenin and galectin-3 levels (Dong, Shim, Hyeon, Lee, & Ryu, 2015;.…”

FRAT1 expression regulates proliferation in colon cancer cells

“…The Wnt/β-catenin pathway is thought to be central to the process of carcinogenesis in CRC (11)(12)(13). Recently, a novel proto-oncogene, frequently rearranged in advanced T-cell lymphomas 1 (FRAT1), has increasingly received attention.…”