Two Natural <i>ent</i>-kauranoids as Novel Wnt Signaling Inhibitors

doi:10.1007/s13659-014-0016-4

Natural Products and Bioprospecting

2014, Vol. 4

Issue (3) : 135-140 DOI: 10.1007/s13659-014-0016-4

Original article

Two Natural ent-kauranoids as Novel Wnt Signaling Inhibitors

Jing Zhang^1,3, Ling-Mei Kong^1,3, Rui Zhan¹, Zhen-Nan Ye^1,3, Jian-Xin Pu¹, Han-Dong Sun¹, Yan Li^1,2

1. State Key Laboratory of Phytochemistry and Plant resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, Yunnan, China;
2. University of Chinese Academy of Science, Beijing 100049, China

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Abstract Constitutively active Wnt signaling frequently occurs in most colon cancers. Therefore, inhibitors of Wnt signaling pathway could provide rational therapeutic effects for colorectal malignancy. Within this paper, we identified two inhibitors of Wnt signaling pathway, rabdoternin B and maoecrystal I from a natural ent-kauranoid library by a dualluciferase reporter gene assay. The two compounds inhibited Wnt signaling pathway in a concentration-dependent manner and exhibited selective cytotoxicity toward a number of colon carcinoma cell lines SW480, HCT116, and HT29, with only weak cytotoxicity towards the normal colonic epithelial cell line CCD-841-CoN. Rabdoternin B and maoecrystal I treatment induced G2/M phase arrest efficiently in SW480 cells as revealed by flow cytometry analysis. A further study found that maoecrystal I decreased the expression of Wnt signaling target genes, including c-myc, cyclin D1, survivin and Axin2 in colon cancer cells. Collectively our data suggests that rabdoternin B and maoecrystal I are novel inhibitors of canonical Wnt signaling pathway and may possess potentials for colon cancer therapy.

Keywords Natural ent-kauranoids Wnt signaling Inhibitors Colon cancer

Fund:This work was supported financially by the hundreds top talents program from Chinese Academy of Sciences, the NSFC(No. 81173076, 21322204), and the projects of science and technology of Yunnan Province(2009C1120, 2013FA047).

Issue Date: 11 February 2018

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Jing Zhang,Ling-Mei Kong,Rui Zhan, et al. Two Natural ent-kauranoids as Novel Wnt Signaling Inhibitors[J]. Natural Products and Bioprospecting, 2014, 4(3): 135-140.

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http://npb.kib.ac.cn/EN/10.1007/s13659-014-0016-4 OR http://npb.kib.ac.cn/EN/Y2014/V4/I3/135

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