Anti-Proliferative Activity of Nodosin, a Diterpenoid from Isodon serra, via Regulation of Wnt/β-Catenin Signaling Pathways in Human Colon Cancer Cells
Autor: | Young-Mi Kim, Hyen Joo Park, Donghwa Kim, Woong Sub Byun, Eun Seo Bae, Sang Kook Lee, Young-Won Chin |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Wnt/β-catenin signaling pathway Colorectal cancer Apoptosis Biology Biochemistry Isodon serra 03 medical and health sciences 0302 clinical medicine Cyclin D1 Nodosin Drug Discovery Survivin AXIN2 medicine Colon cancer cells Pharmacology HEK 293 cells Wnt signaling pathway medicine.disease digestive system diseases 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article Signal transduction Anti-proliferative activity |
Zdroj: | Biomolecules & Therapeutics |
ISSN: | 2005-4483 1976-9148 |
Popis: | Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G2/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway. |
Databáze: | OpenAIRE |
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