Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(11), С. 9091 - 9103
Опубликована: Май 23, 2024
Induction of cuproptosis and targeting multiple signaling pathways show promising applications in tumor therapy. In this study, we synthesized two thiosemicarbazone-copper complexes ([Cu
Язык: Английский
Nature Reviews Clinical Oncology, Год журнала: 2024, Номер 21(5), С. 370 - 388
Опубликована: Март 14, 2024
Язык: Английский
Процитировано
110
Drug Resistance Updates, Год журнала: 2023, Номер 72, С. 101018 - 101018
Опубликована: Ноя. 11, 2023
Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role copper and triggered in pathogenesis cancers have attracted attentions. has garnered enormous interest cancer research communities because its great potential for therapy. Copper-based treatment exerts an inhibiting tumor growth may open door chemotherapy-insensitive tumors. In this review, we provide critical analysis on homeostasis dysregulation development progression cancers. Then core molecular mechanisms cuproptosis discussed, followed summarizing current understanding copper-based agents (copper chelators, ionophores, complexes-based dynamic therapy) treatment. Additionally, summarize emerging data ionophores to subdue chemotherapy resistance different types We also review small-molecule compounds nanoparticles (NPs) that kill cells inducing cuproptosis, which will shed new light anticancer drugs through future. Finally, important concepts pressing questions future should be focused were discussed. This article suggests targeting could novel antitumor therapy strategy overcome drug resistance.
Язык: Английский
Процитировано
95
Frontiers in Oncology, Год журнала: 2023, Номер 13
Опубликована: Июнь 23, 2023
As an essential nutrient, copper’s redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity treat copper-sensitive may offer new strategies for specific disease treatments. In particular, concentration is typically higher in cancer cells, making a critical limiting nutrient cell growth proliferation. Hence, intervening metabolism cells become potential tumor treatment strategy, directly impacting metastasis. this review, we discuss body summarize research progress on role promoting inducing programmed death Additionally, elucidate copper-related drugs treatment, intending provide perspectives treatment.
Язык: Английский
Процитировано
54
Immunological Reviews, Год журнала: 2023, Номер 321(1), С. 211 - 227
Опубликована: Сен. 16, 2023
Summary Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), which correlates to mitochondrial tricarboxylic acid (TCA) cycle, resulting proteotoxic stress eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts indispensable role cancer progression, considered promising strategy therapy. Cancer immunotherapy has gained extensive attention owing breakthroughs immune checkpoint blockade; furthermore, cuproptosis strongly connected modulation antitumor immunity. Thus, thorough recognition concerning mechanisms involved metabolism may facilitate improvement management. This review outlines cellular molecular characteristics links regulated modality with human cancers. We also current knowledge on complex effects immunity response. Furthermore, potential agents that elicit pathways are summarized. Lastly, we discuss influence induction tumor microenvironment as well challenges adding regulators therapeutic strategies beyond traditional
Язык: Английский
Процитировано
51
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116115 - 116115
Опубликована: Янв. 5, 2024
Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms occurrence, metabolism, signaling pathways, drug resistance. Notably, it is now understood that these processes play crucial roles regulating physiological pathological processes, especially tumor development. Consequently, ferroptosis cuproptosis have gained increasing significance as potential targets for anti-cancer This article systematically outlines the molecular mechanisms cross-talk components both elucidating their impacts on cancer. Furthermore, investigates clinical perspective targeted cancer chemotherapy, immunotherapy, radiotherapy. Our discussion extends to a comparative analysis nanoparticles developed based cancer, contrasting them with current conventional therapies. Opportunities challenges treatment explored, emphasizing therapeutic direction co-targeting cuproptosis. The also attempts analyze applications this approach while summarizing existing barriers require overcoming.
Язык: Английский
Процитировано
45
Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(18)
Опубликована: Фев. 23, 2024
Abstract Single‐atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task precisely conduct catalysis at tumor after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations SAzymes anticancer application are still its infancy need be developed. Herein, an situ synthesis strategy Cu was constructed convert adsorbed copper ions into isolated atoms anchored by oxygen (Cu−O 2 /Cu−O 4 ) via GSH‐responsive deformability supports. Our results suggest that activation process could further facilitate dissociation consumption glutathione, thereby leading deposition cytoplasm triggering cuproptosis. peroxidase‐like activity enabled intracellular reactive species production, resulting specifically disturbance metabolism pathway. Meanwhile, exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block glycose uptake boost cuproptosis efficacy. Overall, this effectively diminished off‐target effects SACs‐induced therapies introduced promising paradigm advancing cuproptosis‐associated therapies.
Язык: Английский
Процитировано
35
npj Precision Oncology, Год журнала: 2024, Номер 8(1)
Опубликована: Фев. 26, 2024
Abstract Cancer cell growth, metastasis, and drug resistance pose significant challenges in the management of lung adenocarcinoma (LUAD). However, there is a deficiency optimal predictive models capable accurately forecasting patient prognoses guiding selection targeted treatments. Programmed death (PCD) pathways play pivotal role development progression various cancers, offering potential as prognostic indicators sensitivity markers for LUAD patients. The validation were conducted by integrating 13 PCD patterns with comprehensive analysis bulk RNA, single-cell RNA transcriptomics, pertinent clinicopathological details derived from TCGA-LUAD six GEO datasets. Utilizing machine learning algorithms, we identified ten critical differentially expressed genes associated LUAD, namely CHEK2, KRT18, RRM2, GAPDH, MMP1, CHRNA5, TMPRSS4, ITGB4, CD79A, CTLA4. Subsequently, programmed index (PCDI) based on these across aforementioned cohorts integrated this relevant clinical features to develop several nomograms. Furthermore, observed correlation between PCDI immune including infiltration expression checkpoint molecules. Additionally, found that patients high score may exhibit immunotherapy standard adjuvant chemotherapy regimens; however, they benefit other FDA-supported drugs such docetaxel dasatinib. In conclusion, holds signature can facilitate personalized treatment
Язык: Английский
Процитировано
35
Current Medical Science, Год журнала: 2024, Номер 44(1), С. 28 - 50
Опубликована: Фев. 1, 2024
Abstract Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, body maintains copper homeostasis. deficiency or excess can adversely affect cellular function. Therefore, homeostasis stringently regulated. Recent studies suggest that trigger specific form of cell death, namely, cuproptosis, which triggered by excessive levels intracellular copper. Cuproptosis induces aggregation mitochondrial lipoylated proteins, loss iron-sulfur cluster proteins. In neurodegenerative diseases, pathogenesis progression neurological disorders are linked to This review summarizes advances cuproptosis nervous system diseases. offers research perspectives provide new insights into targeted treatment diseases based on cuproptosis.
Язык: Английский
Процитировано
27
Journal of Cancer Research and Clinical Oncology, Год журнала: 2024, Номер 150(4)
Опубликована: Апрель 25, 2024
Abstract Copper is a necessary micronutrient for maintaining the well-being of human body. The biological activity organic ligands, especially their anticancer activity, often enhanced when they coordinate with copper(I) and (II) ions. its compounds are capable inducing tumor cell death through various mechanisms action, including activation apoptosis signaling pathways by reactive oxygen species (ROS), inhibition angiogenesis, induction cuproptosis, paraptosis. Some copper complexes currently being evaluated in clinical trials ability to map hypoxia cancers, locally advanced rectal cancer bulky tumors. Several studies have shown that nanoparticles can be used as effective agents chemodynamic therapy, phototherapy, hyperthermia, immunotherapy. Despite promising copper-based compounds, use subject certain limitations. Elevated concentrations may promote growth, metastasis affecting cellular processes.
Язык: Английский
Процитировано
23
Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)
Опубликована: Апрель 22, 2024
Abstract Background Postoperative cognitive dysfunction (POCD) is a common neurological complication of anesthesia and surgery in aging individuals. Neuroinflammation has been identified as hallmark POCD. However, safe effective treatments POCD are still lacking. Itaconate an immunoregulatory metabolite derived from the tricarboxylic acid cycle that exerts anti-inflammatory effects by activating nuclear factor erythroid 2-related 2 (Nrf2) pathway. In this study, we investigated underlying mechanism 4-octyl itaconate (OI), cell-permeable derivative, on aged mice. Methods A animal model was established performing aseptic laparotomy 18-month-old male C57BL/6 mice under isoflurane while maintaining spontaneous ventilation. OI intraperitoneally injected into after surgery. Primary microglia neurons were isolated treated to lipopolysaccharide (LPS), isoflurane, OI. Cognitive function, neuroinflammatory responses, well levels gut microbiota their metabolites evaluated. To determine mechanisms therapeutic POCD, ML385, antagonist Nrf2, administered intraperitoneally. endogenous neurogenesis, neuronal apoptosis, Nrf2/extracellular signal-related kinases (ERK) signaling pathway Results Our findings revealed treatment significantly alleviated anesthesia/surgery-induced impairment, concomitant with reduced cytokines IL-1β IL-6, suppressed activation astrocytes hippocampus. Similarly, inhibited expression IL-6 LPS isoflurane-induced primary vitro. Intraperitoneal administration led alterations promoted production microbiota-derived associated neurogenesis. We further confirmed neurogenesis apoptosis hippocampal dentate gyrus Mechanistically, observed decrease Nrf2 both vitro vivo, which reversed treatment. found required for inhibit neuroinflammation The enhanced recovery promotion triggered exposure were, at least partially, mediated Nrf2/ERK Conclusions demonstrate can attenuate impairment stabilizing restrict promote Boosting or supplementation exogenous derivatives may represent novel strategies
Язык: Английский
Процитировано
22