期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 10, 期 5, 页码 732-736出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.8b00624
关键词
Anthraquinone; paraptosis; ER stress; noncaspase-dependent cell death; vacuolation
资金
- National Natural Science Foundation of China [81460561]
Novel anthraquinone compounds that induce ER stress and paraptosis-like cell death were designed and synthesized. Compound 4a is the first organic micromolecule to kill tumor cells by only paraptosis, and its mechanism of action has been further explored. Paraptosis does not appear to involve either phosphatidylserine translocation associated with apoptosis or cell cycle arrest. The bisbenzyloxy and N-(2-hydroxyethyl)formamide structures may be two critical pharmacophores for paraptosis. Bisbenzyloxy can induce ER stress, and the N-(2-hydroxyethyl)formamide structure can increase the ratio of LC3II/I and cytoplasmic vacuolization and facilitates paraptosis. Some antitumor drugs fail to eradicate malignant cell lines with impaired apoptotic pathways; paraptosis may be a route to kill such cells and provides a new potential strategy for cancer chemotherapy.
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