Restraining Cancer Cells by Dual Metabolic Inhibition with a Mitochondrion‐Targeted Platinum(II) Complex

Wang, Kun; Zhu, Chengcheng; He, Yafeng; Zhang, Zhenqin; Zhou, Wen; Nafees, Muhammad; Guo, Yan; Wang, Xiaoyong; Guo, Zijian

doi:10.1002/anie.201900387

Cited by 132 publications

(92 citation statements)

References 40 publications

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“…[3] As the apoptotic machinery is composed of dozens of antiapoptotic and proapoptotic proteins, which are also affected by many oncogenic signals,itishighly difficult to treat cancers with apoptotic resistance.T he apoptotic resistance of cancer cells can, however, be circumvented by chemotherapeutic agents which induce non-apoptotic cell death. [4] Necrosis was originally considered to be random and unregulated, however, increasing evidence reveals that necrosis can be induced and proceed in aregulated manner like apoptosis.T his is known as necroptosis.N ecroptosis is intricately connected with many physiological processes and crucial for the maintenance of tissue homeostasis-throughout life. [5] Reports on necroptosis-inducing chemotherapeutic agents are rare,e specially metal-based agents.C isplatin can trigger necrosis in many types of cancer cells.This occurs only in the presence of the caspase inhibitor (Z-VAD-FMK) however, indicating that necroptosis is optimally induced when the apoptotic machinery is compromised.…”

Section: Introductionmentioning

confidence: 99%

Necroptosis Induced by Ruthenium(II) Complexes as Dual Catalytic Inhibitors of Topoisomerase I/II

et al. 2020

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Inducing necroptosis in cancer cells is an effective approach to circumvent drug‐resistance. Metal‐based triggers have, however, rarely been reported. Ruthenium(II) complexes containing 1,1‐(pyrazin‐2‐yl)pyreno[4,5‐e][1,2,4]triazine were developed with a series of different ancillary ligands (Ru1‐7). The combination of the main ligand with bipyridyl and phenylpyridyl ligands endows Ru7 with superior nucleus‐targeting properties. As a rare dual catalytic inhibitor, Ru7 effectively inhibits the endogenous activities of topoisomerase (topo) I and II and kills cancer cells by necroptosis. The cell signaling pathway from topo inhibition to necroptosis was elucidated. Furthermore, Ru7 displays significant antitumor activity against drug‐resistant cancer cells in vivo. To the best of our knowledge, Ru7 is the first Ru‐based necroptosis‐inducing chemotherapeutic agent.

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Section: Introductionmentioning

confidence: 99%

Necroptosis Induced by Ruthenium(II) Complexes as Dual Catalytic Inhibitors of Topoisomerase I/II

et al. 2020

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“…As one of the most important members of the redox control system, the Trx system can be oxidized by abundant reactive oxygen species (ROS) . Cancer cells are exposed to moderate ROS, mainly because of the active metabolism to oncogenic signals .…”

Section: Introductionmentioning

confidence: 99%

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

Bian

Sun

Liu

et al. 2020

Chemistry A European J

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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.

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“…Redox homeostasis in subcellular compartments, especially mitochondria, is playing a pivotal role in regulating numerous biological processes, including biosynthesis, gene expression, and apoptosis, via key signaling species, such as ROS and GSH . Mitochondrial redox homeostasis is the underlying goal for cancer treatment, because GSH depletion can lead to rapid ROS accumulation, thereby inducing cancer‐cell apoptosis . Recently, SACs revealed high potential in depleting GSH as the SACs with atomically dispersed active sites could prominently improve the metal atom utilization efficiency and enhance the selectivity of biochemical reaction between Au atoms and GSH .…”

Section: Biomedical Applications Of Sacsmentioning

confidence: 99%

Single‐Atom Catalysts in Catalytic Biomedicine

2020

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The intrinsic deficiencies of nanoparticle‐initiated catalysis for biomedical applications promote the fast development of alternative versatile theranostic modalities. The catalytic performance and selectivity are the critical issues that are challenging to be augmented and optimized in biological conditions. Single‐atom catalysts (SACs) featuring atomically dispersed single metal atoms have emerged as one of the most explored catalysts in biomedicine recently due to their preeminent catalytic activity and superior selectivity distinct from their nanosized counterparts. Herein, an overview of the pivotal significance of SACs and some underlying critical issues that need to be addressed is provided, with a specific focus on their versatile biomedical applications. Their fabrication strategies, surface engineering, and structural characterizations are discussed briefly. In particular, the catalytic performance of SACs in triggering some representative catalytic reactions for providing the fundamentals of biomedical use is discussed. A sequence of representative paradigms is summarized on the successful construction of SACs for varied biomedical applications (e.g., cancer treatment, wound disinfection, biosensing, and oxidative‐stress cytoprotection) with an emphasis on uncovering the intrinsic catalytic mechanisms and understanding the underlying structure–performance relationships. Finally, opportunities and challenges faced in the future development of SACs‐triggered catalysis for biomedical use are discussed and outlooked.

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Restraining Cancer Cells by Dual Metabolic Inhibition with a Mitochondrion‐Targeted Platinum(II) Complex

Cited by 132 publications

References 40 publications

Necroptosis Induced by Ruthenium(II) Complexes as Dual Catalytic Inhibitors of Topoisomerase I/II

Necroptosis Induced by Ruthenium(II) Complexes as Dual Catalytic Inhibitors of Topoisomerase I/II

A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS

Single‐Atom Catalysts in Catalytic Biomedicine

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