ATPase Copper Transporting Beta (ATP7B) Is a Novel Target for Improving the Therapeutic Efficacy of Docetaxel by Disulfiram/Copper in Human Prostate Cancer DOI

Liankun Song,

Vyvyan Nguyen, Jun Xie

et al.

Molecular Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 23(6), P. 854 - 863

Published: Feb. 28, 2024

Docetaxel has been the standard first-line chemotherapy for lethal metastatic prostate cancer (mPCa) since 2004, but resistance to docetaxel treatment is common. The molecular mechanisms of remain largely unknown and could be amenable interventions that mitigate resistance. We have recently discovered several docetaxel-resistant mPCa cell lines exhibit lower uptake cellular copper uniquely express higher levels a exporter protein ATP7B. Knockdown ATP7B by silencing RNAs (siRNA) sensitized cells growth-inhibitory apoptotic effects docetaxel. Importantly, deletions in human tissues predict significantly better survival patients after their first than those with wild-type (P = 0.0006). In addition, disulfiram (DSF), an FDA-approved drug alcohol dependence, combination copper, enhanced vivo antitumor xenograft tumor model. Our analyses also revealed DSF engaged decrease COMM domain-containing 1 (COMMD1), S-phase kinase-associated 2 (Skp2), clusterin markedly increase expression cyclin-dependent kinase inhibitor (p21/WAF1). Taken together, our results indicate copper-dependent nutrient vulnerability through improving therapeutic efficacy

Language: Английский

Cuproptosis: Harnessing Transition Metal for Cancer Therapy DOI
Wuyin Wang, Wentao Mo, Zishan Hang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19581 - 19599

Published: Oct. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Language: Английский

Citations

82
Cope with copper: From copper linked mechanisms to copper-based clinical cancer therapies DOI
Xidi Wang, Miao Zhou, Yu Liu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 561, P. 216157 - 216157

Published: April 1, 2023

Language: Английский

Citations

77
Mitochondrial copper in human genetic disorders DOI Creative Commons
Natalie M. Garza, Abhinav B. Swaminathan, Krishna P. Maremanda

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2022, Volume and Issue: 34(1), P. 21 - 33

Published: Nov. 23, 2022

Language: Английский

Citations

70
Small-Molecule Fluorescent Probes for Binding- and Activity-Based Sensing of Redox-Active Biological Metals DOI
Karandeep Grover, Alla A. Koblova, Aidan T. Pezacki

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(9), P. 5846 - 5929

Published: April 24, 2024

Although transition metals constitute less than 0.1% of the total mass within a human body, they have substantial impact on fundamental biological processes across all kingdoms life. Indeed, these nutrients play crucial roles in physiological functions enzymes, with redox properties many being essential to their activity. At same time, imbalances metal pools can be detrimental health. Modern analytical techniques are helping illuminate workings homeostasis at molecular and atomic level, spatial localization real implications dysregulation disease pathogenesis. Fluorescence microscopy has proven one most promising non-invasive methods for studying samples. The accuracy sensitivity bioimaging experiments predominantly determined by fluorescent metal-responsive sensor, highlighting importance rational probe design such measurements. This review covers activity- binding-based sensors that been applied cellular studies. We focus redox-active metals: iron, copper, manganese, cobalt, chromium, nickel. aim encourage further targeted efforts developing innovative approaches understanding chemistry metals.

Language: Английский

Citations

26
Metalloallostery and Transition Metal Signaling: Bioinorganic Copper Chemistry Beyond Active Sites DOI Creative Commons
Vanha N. Pham, Christopher J. Chang

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(11)

Published: Jan. 18, 2023

Transition metal chemistry is essential to life, where binding DNA, RNA, and proteins underpins all facets of the central dogma biology. In this context, metals in are typically studied as static active site cofactors. However, emergence transition signaling, mobile pools can transiently bind biological targets beyond sites, expanding conventional view bioinorganic chemistry. This Minireview focuses on concept metalloallostery, using copper a canonical example how regulate protein function by remote allosteric sites (e.g., exosites). We summarize advances prospects for field, including imaging dynamic signaling pools, inhibition or activation binding, metal-dependent pathways that underlie nutrient vulnerabilities diseases spanning obesity, fatty liver disease, cancer, neurodegeneration.

Language: Английский

Citations

34
Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain DOI
Jianping Zhu, Marcus E. Graziotto,

Veronica Cottam

et al.

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(6), P. 2858 - 2868

Published: May 24, 2024

Copper participates in a range of critical functions the nervous system and human brain. Disturbances brain copper content is strongly associated with neurological diseases. For example, changes level distribution are reported neuroblastoma, Alzheimer's disease, Lewy body disorders, such as Parkinson disease dementia bodies (DLB). There need for more sensitive techniques to measure intracellular levels have better understanding role homeostasis neuronal disorders. Here, we report reaction-based near-infrared (NIR) ratiometric fluorescent probe

Language: Английский

Citations

15
Chalcogen-based fluorescent probes for metal ion detection: Principles, applications, and design strategies DOI
Yuning Liu, Yandong Zhang, Xiaowei Jiang

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 513, P. 215896 - 215896

Published: May 3, 2024

Language: Английский

Citations

13
Recent advances in self‐immobilizing fluorescent probes for in vivo imaging DOI Creative Commons
Yong Zhang,

Xuemei Lv,

Yafu Wang

et al.

Smart Molecules, Journal Year: 2024, Volume and Issue: 2(3)

Published: Aug. 23, 2024

Abstract In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events disease diagnosis. The utilization versatile fluorescent probes in fluorescence imaging offers a powerful tool vivo biomarkers closely associated pathological conditions. However, the dynamic behavior leading to rapid clearance small molecule from regions interest severely compromises their potential imaging. Notably, self‐immobilizing that selectively recognize diseased tissues while improving retention enrichment enable accurate high‐fidelity this review, we aim summarize strategies employed recent advances performance precision using techniques. Lastly, discuss prospects challenges promote further development application more delicate probes.

Language: Английский

Citations

13
A Small‐Molecule Ratiometric Photoacoustic Probe for the High‐Spatiotemporal‐Resolution Imaging of Copper(II) Dynamics in the Mouse Brain DOI
Zhiyong Jiang, Changli Zhang, Xiaoqing Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(13)

Published: Feb. 2, 2024

Copper dysmetabolism is associated with various neurodegenerative disorders, making high-spatiotemporal-resolution imaging of Cu

Language: Английский

Citations

12
MAMMALIAN COPPER HOMEOSTASIS: PHYSIOLOGIC ROLES AND MOLECULAR MECHANISMS DOI
Svetlana Lutsenko, Shubhrajit Roy, Peter Tsvetkov

et al.

Physiological Reviews, Journal Year: 2024, Volume and Issue: 105(1), P. 441 - 491

Published: Aug. 22, 2024

In the past decade, evidence for numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries Cu involvement cell signaling, autophagy, motility, differentiation, and regulated death (cuproptosis) have markedly extended list already known functions Cu, such as a cofactor essential metabolic enzymes, protein structural component, regulator trafficking. Novel unexpected transporting proteins enzymes been identified, new disorders homeostasis described. Significant progress made mechanistic studies two classic metabolism, Menkes disease Wilson’s disease, which paved way novel approaches to their treatment. discovery cuproptosis role metastatic growth increased interest targeting homeostatic pathways treat cancer. this review, we summarize established concepts field discuss how decade expand modify these concepts. brain metabolism functional speciation recently discovered attracted significant attention are highlighted review.

Language: Английский

Citations

10