Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2alpha/ATF4 and IRE1alpha.
Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2alpha/ATF4 and IRE1alpha.
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DOI：
10.1155/2019/3480569
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Md Tohid, Siti Farah
中科院分区：
文献类型：
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作者：
Md Nesran, Zarith Nameyrra;Shafie, Nurul Husna;Md Tohid, Siti Farah
表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶成分中最丰富的生物活性多酚化合物，在结直肠癌（CRC）研究中已被确定为潜在的抗癌剂。本研究旨在确定EGCG靶向CRC内质网（ER）应激通路的作用机制。采用MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑）法测定HT-29细胞株和正常细胞株（3T3） EGCG的毒性。western blot观察内质网应激通路相关蛋白的表达情况。采用Caspase 3/7法检测EGCG诱导的细胞凋亡。结果表明，EGCG处理对HT-29细胞系具有毒性。EGCG通过上调免疫球蛋白结合蛋白（BiP）、pkr样内质网激酶（PERK）、真核起始因子2 α亚基（eif2 α）磷酸化、激活转录因子4 （ATF4）和肌醇要求激酶1 α (ire1 α)诱导HT-29内质网应激。EGCG处理后HT-29细胞可诱导凋亡，Caspase 3/7活性可见。本研究提示绿茶EGCG具有通过诱导内质网应激抑制结直肠癌细胞的潜力。
Epigallocatechin-3-gallate (EGCG) is the most abundant bioactive polyphenolic compound among the green tea constituents and has been identified as a potential anticancer agent in colorectal cancer (CRC) studies. This study was aimed to determine the mechanism of actions of EGCG when targeting the endoplasmic reticulum (ER) stress pathway in CRC. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed on HT-29 cell line and normal cell line (3T3) to determine the EGCG toxicity. Next, western blot was done to observe the expression of the related proteins for the ER stress pathway. The Caspase 3/7 assay was performed to determine the apoptosis induced by EGCG. The results demonstrated that EGCG treatment was toxic to the HT-29 cell line. EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2alpha), activating transcription 4 (ATF4), and inositol-requiring kinase 1 alpha (IRE1alpha). Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity. This study indicates that green tea EGCG has the potential to inhibit colorectal cancer cells through the induction of ER stress.