Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to furthero xidative impairment triggered by agentsg enerating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be ap romising anticancer strategy.H erein, it is shown that ag old(I) complex containing an oleanolic acid derivative (4b)i nduces apopto-sis of ovarian cancerA 2780 cells by activatinge ndoplasmic reticulum stress (ERS). It can inhibitT rxR enzymea ctivity to elevateR OS, mediate ERS and mitochondriald ysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably,t his complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues.[a] Dr.[ + + ] These authors contributed equally to this work.[**] ERS:e ndoplasmic reticulums tress, ROS:r eactive oxygen species, TrxR:t hioredoxin reductase.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

Immunogenic cell death (ICD) can engage a specific immune response and establish a long-term immunity in hepatocellular carcinoma (HCC). Herein, we design and synthesize a series of Pt­(II)-N-heterocyclic carbene (Pt­(II)-NHC) complexes derived from 4,5-diarylimidazole, which show strong anticancer activities in vitro. Among them, 2c displays much higher anticancer activities than cisplatin and other Pt­(II)-NHC complexes, especially in HCC cancer cells. In addition, we find that 2c is a type II ICD inducer, which can successfully induce endoplasmic reticulum stress (ERS) accompanied by reactive oxygen species (ROS) generation and finally lead to the release of damage-associated molecular patterns (DAMPs) in HCC cells. Importantly, 2c shows a great anti-HCC potential in a vaccination mouse model and leads to the in vivo immune cell activation in the CCl4-induced liver injury model.

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