期刊
EUROPEAN JOURNAL OF CANCER PREVENTION
卷 21, 期 5, 页码 413-422出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CEJ.0b013e32834ef16f
关键词
CDK4; CDK6; cell cycle; c-Myc; inhibition of proliferation; ursodeoxycholic acid
类别
资金
- DFG [Ha 1520/17-1]
- Falk Foundation
- Monika Kutzner Stiftung
- Braun Stiftung
Ursodeoxycholic acid (UDCA) can prevent chemical and colitis-associated colon carcinogenesis by unknown mechanism(s). One of the processes underlying the chemopreventive action could be the inhibition of proliferation by UDCA. To clarify the antiproliferative mechanism of UDCA, we used p53(wt) colon carcinoma cell lines HCT8 and HCT116. UDCA-induced inhibition of proliferation was reversible and was associated with a decrease of the S-phase and an increase of G1 phase population, but not with apoptosis or senescence. The treatment suppressed the expression of c-Myc protein and, as a consequence, of several cell cycle regulatory molecules, including CDK4 and CDK6. Using the HCT8 cell line as a model, we show that UDCA suppresses c-Myc at the protein level. The suppression of c-Myc alone or a simultaneous suppression of CDK4 and of CDK6 kinase is sufficient to inhibit cell proliferation. In sum, we identified c-Myc as a primary UDCA target in colon carcinoma cells. The degradation of c-Myc protein decreases the expression of the cell cycle regulators CDK4 and CDK6, which reversibly slows down the cell cycle. The suppression of these proproliferatory molecules is the likely initial mechanism of antiproliferatory action of UDCA on colon cancer cells. European Journal of Cancer Prevention 21:413-422 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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