Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells.
Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells.
复制标题
DOI：
10.1016/j.jnutbio.2011.03.009
复制
发表时间：
2012-06
影响因子：
5.6
通讯作者：
Baek, Seung Joan
中科院分区：
文献类型：
--
作者：
Lee, Seong-Ho;Richardson, Raphael L.;Dashwood, Roderick H.;Baek, Seung Joan
辣椒素是红辣椒中的一种辛辣成分，与抑制各种癌细胞的生长有关。然而，辣椒素诱导癌细胞生长停滞和凋亡的潜在机制尚未完全了解。在本研究中，我们研究了辣椒素是否在体外改变人结直肠癌细胞中β-连环蛋白依赖的信号传导。SW 480、LoVo和HCT-116细胞暴露于辣椒素抑制细胞增殖。用β-catenin/T-cell factor（TCF）应答报告基因瞬时转染表明辣椒素抑制β-catenin/TCF的转录活性。辣椒素处理导致细胞内β-连环蛋白水平降低和β-连环蛋白基因（CTNNB 1）转录物减少。这些结果通过由含有Catnb基因的启动子区的启动子-报告基因构建体驱动的降低的荧光素酶报告基因活性来证实。此外，辣椒素通过增强蛋白酶体依赖性降解使β-连环蛋白不稳定。Western blot和免疫沉淀研究表明辣椒素处理抑制了TCF-4的表达，并破坏了TCF-4和β-catenin的相互作用。这项研究确定了β-catenin/TCF依赖性途径的作用，该途径可能有助于辣椒素在人类结直肠癌细胞中的抗癌活性。
Capsaicin is a pungent ingredient in chili red peppers and has been linked to suppression of growth in various cancer cells. However, the underlying mechanism(s) by which capsaicin induces growth arrest and apoptosis of cancer cells is not completely understood. In the present study, we investigated whether capsaicin alters β-catenin-dependent signaling in human colorectal cancer cells in vitro. Exposure of SW480, LoVo, and HCT-116 cells to capsaicin suppressed cell proliferation. Transient transfection with a β-catenin/T-cell factor (TCF)-responsive reporter indicated that capsaicin suppressed the transcriptional activity of β-catenin/TCF. Capsaicin treatment resulted in a decrease of intracellular β-catenin levels and a reduction of transcripts from the β-catenin gene (CTNNB1). These results were confirmed by a reduced luciferase reporter activity driven by promoter-reporter construct containing the promoter region of the Catnb gene. In addition, capsaicin destabilized β-catenin through enhancement of proteosomal-dependent degradation. Western blot and immunoprecipitation studies indicated that capsaicin treatment suppressed TCF-4 expression and disrupted the interaction of TCF-4 and β-catenin. This study identifies a role for the β-catenin/TCF-dependent pathway that potentially contributes to the anti-cancer activity of capsaicin in human colorectal cancer cells.
登录
查看更多内容
影响因子：
6.1
作者：
Chu, YF;Sun, J;Liu, RH
通讯作者：
Liu, RH
影响因子：
3.6
作者：
Huang, JW;Shiau, CW;Chen, CS
通讯作者：
Chen, CS
影响因子：
8
作者：
Lee, S-H;Bahn, J. H.;Whitlock, N. C.;Baek, S. J.
通讯作者：
Baek, S. J.
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R