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http://dx.doi.org/10.4062/biomolther.2020.003

Anti-Proliferative Activity of Nodosin, a Diterpenoid from Isodon serra, via Regulation of Wnt/β-Catenin Signaling Pathways in Human Colon Cancer Cells  

Bae, Eun Seo (College of Pharmacy, Natural Products Research Institute, Seoul National University)
Kim, Young-Mi (College of Pharmacy, Research Institute of Pharmaceutical Science, Seoul National University)
Kim, Dong-Hwa (College of Pharmacy, Natural Products Research Institute, Seoul National University)
Byun, Woong Sub (College of Pharmacy, Natural Products Research Institute, Seoul National University)
Park, Hyen Joo (College of Pharmacy, Natural Products Research Institute, Seoul National University)
Chin, Young-Won (College of Pharmacy, Research Institute of Pharmaceutical Science, Seoul National University)
Lee, Sang Kook (College of Pharmacy, Natural Products Research Institute, Seoul National University)
Publication Information
Biomolecules & Therapeutics / v.28, no.5, 2020 , pp. 465-472 More about this Journal
Abstract
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.
Keywords
Nodosin; Isodon serra; Wnt/${\beta}$-catenin signaling pathway; Anti-proliferative activity; Apoptosis; Colon cancer cells;
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