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脱氢木香内酯和木香烃内酯对结肠癌细胞中Wnt/β-连环蛋白信号通路的抑制作用

Inhibition of Wnt/β-Catenin Pathway by Dehydrocostus Lactone and Costunolide in Colon Cancer Cells.

作者信息

Dong Guang-Zhi, Shim Ah-Ram, Hyeon Jin Seong, Lee Hwa Jin, Ryu Jae-Ha

机构信息

Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.

出版信息

Phytother Res. 2015 May;29(5):680-6. doi: 10.1002/ptr.5299. Epub 2015 Jan 27.

Abstract

Abnormal activation of β-catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β-catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti-colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β-catenin. They also suppressed the nuclear translocation of galectin-3 that is one of the coactivators of β-catenin in SW-480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW-480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti-colorectal cancer activities through inhibiting Wnt/β-catenin pathway.

摘要

据报道,在散发性和遗传性结直肠癌中,90%存在β-连环蛋白的异常激活。抑制异常激活的β-连环蛋白是结直肠癌化学预防和治疗的良好策略之一。在本研究中,我们从木香根部分离出两种主要化合物,去氢木香内酯(DCL)和木香烃内酯(CL),并研究了它们的抗结直肠癌活性。DCL和CL通过抑制β-连环蛋白的核转位来抑制细胞周期蛋白D1和生存素。它们还抑制了半乳糖凝集素-3在SW-480结肠癌细胞中的核转位,而半乳糖凝集素-3是β-连环蛋白的共激活因子之一。此外,DCL和CL通过诱导细胞周期停滞和细胞死亡来抑制SW-480结肠癌细胞的增殖和存活。综上所述,木香根中的DCL和CL通过抑制Wnt/β-连环蛋白通路具有抗结直肠癌活性。

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