Two Natural ent-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 • Next Articles

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

Received:2014-02-25 Revised:2014-02-25 Online:2018-02-11 Published:2014-06-24
Supported by:
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).

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

通讯作者: Han-Dong Sun,e-mail:hdsun@mail.kib.ac.cn;Yan Li,e-mail:liyanb@mail.kib.ac.cn
基金资助:
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).

Abstract

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.

Key words: Natural ent-kauranoids, Wnt signaling, Inhibitors, Colon cancer

摘要： 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.

关键词: Natural ent-kauranoids, Wnt signaling, Inhibitors, Colon cancer

Jing Zhang, Ling-Mei Kong, Rui Zhan, Zhen-Nan Ye, Jian-Xin Pu, Han-Dong Sun, Yan Li. Two Natural ent-kauranoids as Novel Wnt Signaling Inhibitors[J]. Natural Products and Bioprospecting, 2014, 4(3): 135-140.

Jing Zhang, Ling-Mei Kong, Rui Zhan, Zhen-Nan Ye, Jian-Xin Pu, Han-Dong Sun, Yan Li. Two Natural ent-kauranoids as Novel Wnt Signaling Inhibitors[J]. 应用天然产物, 2014, 4(3): 135-140.

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Two Natural ent-kauranoids as Novel Wnt Signaling Inhibitors

Two Natural ent-kauranoids as Novel Wnt Signaling Inhibitors

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