Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells
Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells
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DOI：
10.1002/mc.20374
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发表时间：
2008-03-01
影响因子：
4.6
通讯作者：
Baek, Seung Joon
中科院分区：
文献类型：
--
作者：
Lee, Seong-Ho;Cekanova, Maria;Baek, Seung Joon
6-姜酚是生姜的天然产物，已被认为具有抗肿瘤和促凋亡活性。然而，在人类结直肠癌中，它预防癌症的机制还不是很清楚。细胞周期蛋白D1是一种原癌基因，在许多癌症中过表达，并通过β-连环蛋白信号激活在细胞增殖中发挥作用。非甾体抗炎药(NSAID)激活基因-1(NAG-1)是一种与促凋亡和抗肿瘤相关的细胞因子。在本研究中，我们检测了6-姜酚是否影响细胞周期蛋白D1和NAG-1的表达，并确定了6-姜酚影响体外培养的人结直肠癌细胞生长的机制。6-姜黄素可抑制细胞增殖，诱导细胞凋亡和G期细胞周期停滞。随后，6-姜辣素抑制细胞周期蛋白D1的表达，诱导NAG-1的表达。细胞周期蛋白D 1的抑制与抑制P-连环蛋白转位和细胞周期蛋白D 1蛋白分解有关。此外，使用抑制剂和siRNA转染的实验证实了PKC epsilon和糖原合成酶激酶(GSK)-3β通路参与了6-姜辣素诱导的NAG-1的表达。结果提示，6-姜辣素通过上调NAG-1和G，通过下调细胞周期蛋白D1抑制细胞周期，从而促进细胞凋亡。6-姜酚的作用可能涉及多种机制，包括蛋白质降解以及β-连环素、PKC epsilon和GSK-3β途径。(C)2007年Wiley-Liss，Inc.
6-Gingerol, a natural product of ginger, has been known to possess anti-tumorigenic and pro-apoptotic activities. However, the mechanisms by which it prevents cancer are not well understood in human colorectal cancer. Cyclin D1 is a proto-oncogene that is overexpressed in many cancers and plays a role in cell proliferation through activation by beta-catenin signaling. Nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) is a cytokine associated with pro-apoptotic and anti-tumorigenic properties. In the present study, we examined whether 6-gingerol influences cyclin D1 and NAG-1 expression and determined the mechanisms by which 6-gingerol affects the growth of human colorectal cancer cells in vitro. 6-Gingerol treatment suppressed cell proliferation and induced apoptosis and G, cell cycle arrest. Subsequently, 6-gingerol suppressed cyclin D1 expression and induced NAG-1 expression. Cyclin D1 suppression was related to inhibition of P-catenin translocation and cyclin D1 proteolysis. Furthermore, experiments using inhibitors and siRNA transfection confirm the involvement of the PKC epsilon and glycogen synthase kinase (GSK)-3 beta pathways in 6-gingerol-induced NAG-1 expression. The results suggest that 6-gingerol stimulates apoptosis through upregulation of NAG-1 and G, cell cycle arrest through downregulation of cyclin D1. Multiple mechanisms appear to be involved in 6-gingerol action, including protein degradation as well as beta-catenin, PKC epsilon, and GSK-3 beta pathways. (C) 2007 Wiley-Liss, Inc.