Physalis peruviana-Derived 4 beta-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo
Ye, Zhen-Nan1,2,3; Yuan, Feng1,2; Liu, Jie-Qing1; Peng, Xing-Rong1; An, Tao1; Li, Xue1,2; Kong, Ling-Mei1; Qiu, Ming-Hua1; Li, Yan1
Corresponding AuthorKong, Ling-Mei(konglingmei@mail.kib.ac.cn) ; Qiu, Ming-Hua(mhchiu@mail.kib.ac.cn) ; Li, Yan(liyanb@mail.kib.ac.cn)
2019-03-22
Source PublicationMOLECULES
ISSN1420-3049
Volume24Issue:6Pages:13
AbstractDeregulation of the Wnt signaling pathway leads to colorectal cancer progression. Natural dietary compounds serve as promising candidates for development as chemopreventive agents by suppressing the Wnt/beta-catenin signaling pathway. Physalis peruviana-derived 4 beta HWE showed a significant inhibitory activity with a calculated IC50 of 0.09 mu M in a screening of novel inhibitors of Wnt signaling with the dual-luciferase reporter assay. This study investigated the anti-tumor effect of 4 beta HWE and the potential Wnt signaling inhibitory mechanism. Both the western blot analysis and immunofluorescence assay showed that 4 beta HWE promoted the phosphorylation and degradation of beta-catenin and the subsequent inhibition of its nuclear translocation to attenuate the endogenous Wnt target gene expression in colorectal cancer (CRC) cells. The cell viability assay indicated that 4 beta HWE preferentially inhibited the proliferation of CRC compared with CCD-841-CoN, a normal human colonic epithelial cell line. 4 beta HWE-mediated G0/G1 cell cycle arrest and apoptosis induction contributed to the suppression of the proliferation of CRC in the cell cycle and Annexin V-FITC/Propidium Iodide apoptosis analysis. Moreover, in vivo, 4 beta HWE dramatically inhibited tumor growth in HCT116 xenografts by attenuating the Wnt/beta-catenin signaling pathway. In conclusion, our study suggested that 4 beta HWE could be of potential use in anti-tumor agent development as a novel Wnt signaling inhibitor.
Keyword4 beta HWE Wnt signaling pathway beta-catenin colorectal cancer
DOI10.3390/molecules24061146
Indexed BySCI
Language英语
WOS IDWOS:000464290900008
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/67595
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorKong, Ling-Mei; Qiu, Ming-Hua; Li, Yan
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Jena Univ Hosp, Dept Biochem 2, D-07743 Jena, Germany
Recommended Citation
GB/T 7714
Ye, Zhen-Nan,Yuan, Feng,Liu, Jie-Qing,et al. Physalis peruviana-Derived 4 beta-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo[J]. MOLECULES,2019,24(6):13.
APA Ye, Zhen-Nan.,Yuan, Feng.,Liu, Jie-Qing.,Peng, Xing-Rong.,An, Tao.,...&Li, Yan.(2019).Physalis peruviana-Derived 4 beta-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo.MOLECULES,24(6),13.
MLA Ye, Zhen-Nan,et al."Physalis peruviana-Derived 4 beta-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo".MOLECULES 24.6(2019):13.
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