Novel anthraquinone derivatives trigger endoplasmic reticulum stress response and induce apoptosis

被引:3
作者
Zhai, Honglan [1 ]
Wang, Chunmiao [2 ]
Li, Junying [3 ]
Liang, Dandan [4 ]
Li, Fengming [1 ]
Zhang, Qiuping [1 ]
Wang, Jingni [1 ]
Ma, Tuo [1 ]
Li, Danrong [2 ]
Hou, Huaxin [1 ]
机构
[1] Guangxi Med Univ, Coll Pharm, Nanning 530021, Peoples R China
[2] Guangxi Med Univ, Life Sci Inst, Nanning 530021, Peoples R China
[3] Shanghai Wotai Biotechnol Co Ltd Kunming, Global Registrat & Compliance Dept, Kunming 650101, Peoples R China
[4] Xinjiang Second Med Coll, Sch Pharm, Karamay 834000, Peoples R China
基金
中国国家自然科学基金;
关键词
anthraquinone derivatives; anticancer; apoptosis; endoplasmic reticulum; UNFOLDED PROTEIN RESPONSE; CANCER CELLS; LUNG-CANCER; ER STRESS; AUTOPHAGY; INHIBITOR; ACTIVATION; EFFICACY; POTENT; DEATH;
D O I
10.4155/fmc-2022-0217
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Background: Endoplasmic reticulum (ER) stress is a therapeutic target in cancer given its regulation of bioenergetics and cell death. Methodology & results: We synthesized 14 ER stress-triggered anthraquinone derivatives by introducing an amino group at the 3-position side chain of the lead compound obtained previously. Most of the anthraquinone derivatives exhibited good antitumor activity due to their ability to induce ER damage through cytoplasmic vacuoles. The mechanisms of ER stress caused by compound KA-4c were related to increasing the expression levels of the ATF6 and Bip proteins and upregulating CHOP and cleaved PARP. Conclusion: Compound KA-4c triggers ER stress response and induces apoptosis via the ATF6-CHOP signaling pathway.
引用
收藏
页码:129 / 145
页数:17
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