期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 46, 页码 13150-13155出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1616336113
关键词
prodigiosin; Wnt/beta-catenin signaling; breast cancer; LRP6; Dishevelled (DVL)
资金
- National Nature Science Foundation of China [81372342, 31501143]
- Nature Science Foundation of Guangdong Province [2014A030310168]
- Shenzhen Peacock Innovation Team Project [KQTD20140630100658078]
- Key Laboratory Project of Shenzhen [ZDSY20130329101130496]
- Shenzhen Basic Research Program [JCYJ20150525092941006, JCYJ20150525092941030]
Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/beta-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/beta-catenin pathway. Prodigiosin blocked Wnt/beta-catenin signaling by targeting multiple sites of this pathway, including the low-density lipoprotein-receptor-related protein ( LRP) 6, Dishevelled ( DVL), and glycogen synthase kinase-3 beta ( GSK3 beta). In breast cancer MDA-MB-231 and MDA-MB-468 cells, nanomolar concentrations of prodigiosin decreased phosphorylation of LRP6, DVL2, and GSK3 beta and suppressed beta-catenin-stimulated Wnt target gene expression, including expression of cyclin D1. In MDA-MB-231 breast cancer xenografts andMMTV-Wnt1 transgenic mice, administration of prodigiosin slowed tumor progression and reduced the expression of phosphorylated LRP6, phosphorylated and unphosphorylated DVL2, Ser9 phosphorylated GSK3 beta, active beta-catenin, and cyclin D1. Through its ability to inhibit Wnt/a-catenin signaling and reduce cyclin D1 levels, prodigiosin could have therapeutic activity in advanced breast cancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据