台灣蜂膠衍生物通過誘導內質網應激和激活轉錄因子-3誘導人肝癌細胞凋亡
A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells
版權所有©2013Fat-Moon Suketal.這是根據知識共享署名許可分發的開放獲取文章，其中規定了無限制使用，分發和重新製作，提供了原創性功能。
激活轉錄因子（ATF-）3，一種應激誘導型轉錄因子，在各種應激條件下迅速上調，在誘導癌細胞凋亡中起重要作用.NBM-TP-007-GS-002（GS-002）是一種台灣蜂膠素propolin G（PPG）衍生物。在本研究中，我們在體外研究了人肝癌Hep3B和HepG2細胞中GS-002的抗腫瘤作用。首先，我們發現GS-02顯著抑制細胞增殖並誘導細胞凋亡的劑量依賴性。在GS-002處理的細胞中發現幾種主要的凋亡指標，例如半胱天冬酶-3，半胱天冬酶-9和聚（ADP-核糖）聚合酶（PARP）的切割形式。 GS-002還誘導內質網（ER）激活，如通過ER激活反應蛋白包括葡萄糖調節蛋白78（GRP78），生長停滯和DNA損傷誘導基因153（GADD153），磷酸化脫氧核糖核酸因子2α（eIF2α） ），磷酸化蛋白質內質網 - 宿主激酶（PERK）和ATF-3。 ATF-3表達的誘導是由有絲分裂原激活的蛋白激酶（MAPK），信號轉導通路在COS-002處理的細胞中進行的。此外，我們發現GS-002在ATF-3表達細胞中誘導更多的癌細胞的凋亡。這些結果表明，蜂膠衍生物GS-002的凋亡誘導通過ER脅迫和ATF-3-依賴性通路部分介導，而GS-002具有作為抗腫瘤藥物發展的潛力。
Copyright©2013FatMoon Suketal.This is an open access article distributed under the Creative Commons Attribution License, which permit sunrestricteduse, distribution, and reproduction in any medium, provided the original work is properlycited.
Activating transcription factor-(ATF-) 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis.NBM-TP-007-GS-002(GS-002) is a Taiwanese propolin G (PPG) derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro.First,we found that GS-02 significantly in hibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP). GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153),phosphorylate deukaryoticinitiation factor2𝛼(eIF2𝛼),phosphorylatedproteinendoplasmic-reticular-residentkinase (PERK), and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathwaysinGS-002-treatedcells.Further more,we found that GS-002 induced more cell apoptosis in ATF-3-over expressing cells. These results suggest that the induction of apoptosis by the propolis derivative,GS-002,is partially mediated through ER stress and ATF-3-dependentpathways,andGS-002 has the potential for development as an antitumor drug.
