Alkaloids from nux vomica suppresses colon cancer cell growth through Wnt/β-catenin signaling pathway

被引:33
|
作者
Ren, Hua [1 ]
Zhao, Jianping [1 ]
Fan, Dongsheng [1 ]
Wang, Ze [2 ]
Zhao, Tingjie [3 ]
Li, Yuejin [1 ]
Zhao, Yirui [1 ]
Adelson, David [4 ]
Hao, Huiqin [2 ]
机构
[1] Shanxi Hosp Integrated Tradit & Western Med, Cent Lab, Taiyuan, Shanxi, Peoples R China
[2] Shanxi Univ Chinese Med, Clin Coll Integrated Tradit Chinese & Western Med, Taiyuan 030619, Shanxi, Peoples R China
[3] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Biostat & Data Sci, New Orleans, LA USA
[4] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia
关键词
alkaloids; colon cancer; nux-vomica; Wnt; beta-catenin signaling pathway; IN-VITRO; BRUCINE; STRESS; SEEDS;
D O I
10.1002/ptr.6347
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/beta-catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of beta-catenin, c-Myc, and p-LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.
引用
收藏
页码:1570 / 1578
页数:9
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