B19, a novel monocarbonyl analogue of curcumin, induces human ovarian cancer cell apoptosis via activation of endoplasmic reticulum stress and the autophagy signaling pathway.
B19, a novel monocarbonyl analogue of curcumin, induces human ovarian cancer cell apoptosis via activation of endoplasmic reticulum stress and the autophagy signaling pathway.
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B19 是一种新型姜黄素单羰基类似物，通过激活内质网应激和自噬信号通路诱导人卵巢癌细胞凋亡
DOI：
10.7150/ijbs.5711
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发表时间：
2013
影响因子：
9.2
通讯作者：
Lv J
中科院分区：
文献类型：
--
作者：
Qu W;Xiao J;Zhang H;Chen Q;Wang Z;Shi H;Gong L;Chen J;Liu Y;Cao R;Lv J
背景资料：未折叠蛋白反应、自噬和内质网应激诱导的凋亡调节肿瘤细胞的命运，并已成为开发癌症治疗药物的新信号靶标。在临床试验和研究中，姜黄素已被用于治疗几种不同的癌症，包括卵巢癌;然而，ER应激和自噬在姜黄素和新姜黄素类似物的治疗作用中的作用仍不清楚。方法：MTT法测定细胞活力。PI/Annexin V-FITC染色流式细胞术检测细胞凋亡。免疫印迹分析ER应激和自噬相关蛋白的表达水平。免疫荧光染色检测自噬的激活。结果：B19诱导HO 8910细胞凋亡呈剂量依赖性。我们还确定，这种效应与UPR和ER应激介导的凋亡途径中一系列关键组分的相应增加有关，随后是caspase 3的切割和激活。我们还观察到B19处理诱导HO8910细胞中的自噬。使用3-甲基腺嘌呤（3-MA）抑制自噬增加了细胞内错误折叠蛋白的水平，这增强了卵巢癌细胞凋亡。结论：我们的数据表明，ER应激和自噬可能在上皮性卵巢癌细胞系中由姜黄素类似物B19诱导的细胞凋亡中起作用，并且自噬抑制可以通过诱导严重的ER应激来增加姜黄素类似物诱导的细胞凋亡。
Background: The unfolded protein response, autophagy and endoplasmic reticulum (ER) stress-induced apoptosis regulate tumor cell fate and have become novel signaling targets for the development of cancer therapeutic drugs. Curcumin has been used to treat several different cancers, including ovarian cancer, in clinical trials and research; however, the role of ER stress and autophagy in the therapeutic effects of curcumin and new curcumin analogues remains unclear. Methods: Cell viability was determined using the MTT assay. Apoptosis was detected using flow cytometry with PI/Annexin V-FITC staining. The expression levels of ER stress- and autophagy-related proteins were analyzed by western blotting. The activation of autophagy was detected using immunofluorescence staining. Results: We demonstrated that B19 induced HO8910 cell apoptosis in a dose-responsive manner. We also determined and that this effect was associated with corresponding increases in a series of key components in the UPR and ER stress-mediated apoptosis pathways, followed by caspase 3 cleavage and activation. We also observed that B19 treatment induced autophagy in HO8910 cells. The inhibition of autophagy using 3-methyladenine (3-MA) increased levels of intracellular misfolded proteins, which enhanced ovarian cancer apoptosis. Conclusions: Our data indicate that ER stress and autophagy may play a role in the apoptosis that is induced by the curcumin analogue B19 in an epithelial ovarian cancer cell line and that autophagy inhibition can increase curcumin analogue-induced apoptosis by inducing severe ER stress.
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DOI：
10.1074/jbc.m109.014092
发表时间：
2010-02-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Armstrong JL;Flockhart R;Veal GJ;Lovat PE;Redfern CP
通讯作者：
Redfern CP
影响因子：
12.4
作者：
Criollo, A.;Maiuri, M. C.;Kroemer, G.
通讯作者：
Kroemer, G.
影响因子：
13.3
作者：
Carew, Jennifer S.;Nawrocki, Steffan T.;Cleveland, John L.
通讯作者：
Cleveland, John L.
影响因子：
3.6
作者：
Aoki, Hiroshi;Takada, Yasunari;Kondo, Yasuko
通讯作者：
Kondo, Yasuko
DOI：
10.1084/jem.20110996
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Joubert PE;Werneke SW;de la Calle C;Guivel-Benhassine F;Giodini A;Peduto L;Levine B;Schwartz O;Lenschow DJ;Albert ML
通讯作者：
Albert ML