Biomolecules & Therapeutics  https://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
Eun Seo Bae1, Young-Mi Kim2, Dong-Hwa Kim1, Woong Sub Byun1, Hyen Joo Park1, Young-Won Chin2 and Sang Kook Lee1,*
1College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826,
2College of Pharmacy, Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Republic of Korea
*E-mail: sklee61@snu.ac.kr
Tel: +82-2-880-2475, Fax: +82-2-888-9122
Received: January 13, 2020; Revised: March 31, 2020; Accepted: April 20, 2020; Published online: May 12, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

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/β-catenin signaling pathway, Anti-proliferative activity, Apoptosis, Colon cancer cells


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