Atractylochromene Is a Repressor of Wnt/β-Catenin Signaling in Colon Cancer Cells

Abstract

Wnt/β-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated β-catenin increases the cancer cell proliferation, differentiation and metastasis through increasing the expression of its oncogenic target genes. In this study, we identified an inhibitor of β-catenin dependent Wnt pathway from rhizomes of Atractylodes macrocephala Koidzumi (Compositae). The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed β-catenin/T-cell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-3β. AC down-regulated the nuclear level of β-catenin through the suppression of galectin-3 mediated nuclear translocation of β-catenin in SW-480 colon cancer cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

An hTERT/ZEB1 complex directly regulates E-cadherin to promote epithelial-to-mesenchymal transition (EMT) in colorectal cancer

“…Studies have shown that hTERT promotes tumor invasion and metastasis in gastric cancer, liver cancer, and esophageal cancer [ 24 , 27 , 28 ], and that hTERT promotes EMT through the Wnt signaling pathway in gastric cancer and osteosarcoma [ 8 , 15 ]. However, Wnt signaling is inactivated in some CRC cells [ 9 ], in which we found hTERT expression promotes EMT.…”

“…The canonical Wnt pathway is an important signal that can initiate EMT by triggering β-catenin translocation to the nucleus, where it acts as coactivator of T-cell and lymphoid enhancer (TCF–LEF) factors in target gene transcriptional activation [ 7 ]. While hTERT can promote migration and invasion through the Wnt signaling pathway to induce EMT in gastric cancer [ 8 ], Wnt signal is not activated in some tumors, such as in CRC [ 9 ]. And further study found that HCT116 cells, a CRC cell line, manifested a low Wnt activity [ 10 ].…”

Effect of halometasone cream combined with Simiao pill on the therapeutic effect and expression of serum leukotriene B4 (LTB4) and thymic stromal lymphopoietin (TSLP) in patients with eczema, and the factors influencing its clinical efficacy

“…In Simiao pill, Amur Corktree Bark exhibits antibacterial and anti-inflammatory properties, and plays a role in improving internal circulation, reducing vascular permeability, reducing the release of inflammatory factors, accelerating the growth of granulation tissue, and restoring the skin at the lesions (17). Pharmacological studies (18,19) (20,21). Therefore, Simiao pill combined with halometasone cream can improve clinical symptoms by down-regulating serum LTB4 and TSLP.…”

Effects of complex extracts of traditional Chinese herbs on gastric mucosal injury in rats and potential underlying mechanism

“…RKO reporter cells were seeded in 96‐well plates at a density of 2.0 × 10 4 cells/ well and incubated at 37 °C in 5% CO 2 environment for 12 h. Then, the cells were treated with Wnt activator and 4.5 mg /mL CE1 and CE5 or 4.8 mg /mL CE4 for another 24 h. Luciferase activity was measured with the dual Luciferase Reporter Gene Assay Kit (Promega) according to the manufacturer's instructions. Wnt signaling activity was calculated as fold change (TOP/FOP Luciferase activity) (Shim et al., 2015).…”