Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells.
Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells.
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DOI：
10.4062/biomolther.2016.114
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发表时间：
2017-05-01
影响因子：
3.7
通讯作者：
Jeong JB
中科院分区：
文献类型：
--
作者：
Park GH;Song HM;Jeong JB
咖啡豆醇作为一种咖啡特有的二萜已被报道能诱导人类癌细胞凋亡。虽然已经阐明了咖啡醇介导的细胞凋亡的一些分子靶点，但咖啡醇对细胞凋亡作用的进一步机制尚不清楚。据报道，激活转录因子3 （ATF3）与结直肠癌的细胞凋亡有关。本研究旨在探讨咖啡豆醇刺激人结直肠癌细胞ATF3表达和凋亡的分子机制。咖啡醇增加人结直肠癌细胞凋亡。它还通过转录活性增加了ATF3的表达。咖啡醇激活ATF3转录的顺式元件是位于ATF3启动子- 147至- 85之间的CREB。ATF3过表达增加了咖啡醇介导的PARP裂解，而ATF3敲低则减弱了咖啡醇对PARP的裂解。抑制ERK1/2和GSK3β可阻断咖啡醇介导的ATF3表达。结果表明，咖啡醇通过atf3介导途径诱导人结直肠癌细胞凋亡。
Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of kahweol is not known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells. Kahweol increased apoptosis in human colorectal cancer cells. It also increased ATF3 expression through the transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by kahweol was CREB located between −147 to −85 of ATF3 promoter. ATF3 overexpression increased kahweol-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by kahweol. Inhibition of ERK1/2 and GSK3β blocked kahweol-mediated ATF3 expression. The results suggest that kahweol induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.