Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells DOI Creative Commons

Yahui Ding,

Xiaoping Chen, Can Liu

и другие.

Journal of Hematology & Oncology, Год журнала: 2021, Номер 14(1)

Опубликована: Янв. 20, 2021

Abstract Background TNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of cancer. There an urgent need for identification therapeutic agents unique mode action overcoming current challenges in treatment. Methods Different inhibitors were used to study cell death manner DMOCPTL . RNA silencing was evaluate functions GPX4 ferroptosis apoptosis cells EGR1 apoptosis. Immunohistochemical assay tissue microarray investigating correlation TNBC. Computer-aided docking small molecule probe binding GPX4. Results , a derivative natural product parthenolide, exhibited about 15-fold improvement comparing that parent compound PTL cells. The showed anti-TNBC effect mainly by inducing through ubiquitination indicated induced directly protein. To best our knowledge, this first report Moreover, mechanism regulation still obscure. Here, we firstly reveal regulated mitochondria-mediated Compound 13 prodrug effectively inhibited growth tumor prolonged lifespan mice vivo, no obvious toxicity observed. Conclusions These findings revealed novel induce provided up-regulation deserves further studies as lead ultimate discovery effective drug.

Язык: Английский

Targeting Ferroptosis to Iron Out Cancer DOI Creative Commons

Behrouz Hassannia,

Peter Vandenabeele, Tom Vanden Berghe

и другие.

Cancer Cell, Год журнала: 2019, Номер 35(6), С. 830 - 849

Опубликована: Май 16, 2019

Язык: Английский

Процитировано

1985
Ferroptosis, a new form of cell death: opportunities and challenges in cancer DOI Creative Commons

Yanhua Mou,

Jun Wang, Jinchun Wu

и другие.

Journal of Hematology & Oncology, Год журнала: 2019, Номер 12(1)

Опубликована: Март 29, 2019

Ferroptosis is a novel type of cell death with distinct properties and recognizing functions involved in physical conditions or various diseases including cancers. The fast-growing studies ferroptosis cancer have boosted perspective for its usage therapeutics. Here, we review the current findings regulation especially focus on function ncRNAs mediating process ferroptotic how was relation to other regulated deaths. Aberrant diverse types tissues were summarized, elaborated recent data about actors some "conventional" drugs natural compounds as inducers cancer. Finally, deliberate future orientation cells unsettled issues, which may forward speed clinical use induction treatment.

Язык: Английский

Процитировано

1476
Ferroptosis: machinery and regulation DOI Open Access
Xin Chen, Jingbo Li, Rui Kang

и другие.

Autophagy, Год журнала: 2020, Номер 17(9), С. 2054 - 2081

Опубликована: Авг. 19, 2020

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which controlled integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase the main promoter ferroptosis producing hydroperoxides, its function relies on activation ACSL4-dependent biosynthesis. In contrast, selenium-containing GPX4 currently recognized as a central repressor ferroptosis, activity depends glutathione produced from cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, amino acids) degradation pathways (macroautophagy/autophagy ubiquitin-proteasome system) orchestrate complex ferroptotic response through direct or indirect regulation iron accumulation peroxidation. Although detailed mechanism membrane injury during remains mystery, ESCRT III-mediated plasma repair can make cells resistant to ferroptosis. Here, we review recent rapid progress in understanding molecular mechanisms focus epigenetic, transcriptional, posttranslational this process.Abbreviations: 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear renal carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated acid; RCD: death; RNS: reactive nitrogen species; ROS: oxygen RTAs: radical-trapping antioxidants; UPS: system; UTR: untranslated region.

Язык: Английский

Процитировано

1379
Recent Progress in Ferroptosis Inducers for Cancer Therapy DOI
Chen Liang, Xinglin Zhang, Mengsu Yang

и другие.

Advanced Materials, Год журнала: 2019, Номер 31(51)

Опубликована: Окт. 8, 2019

Abstract Ferroptosis is a newly discovered form of regulated cell death that the nexus between metabolism, redox biology, and human health. Emerging evidence shows potential triggering ferroptosis for cancer therapy, particularly eradicating aggressive malignancies are resistant to traditional therapies. Recently, there has been great deal effort design develop anticancer drugs based on induction. Recent advances ferroptosis‐inducing agents at intersection chemistry, materials science, biology presented. The basis summarized first highlight feasibility characteristics therapy. A literature review inducers (including small molecules nanomaterials) then presented delineate their design, action mechanisms, applications. Finally, some considerations research spotlighted, followed by discussion challenges future development directions this burgeoning field.

Язык: Английский

Процитировано

1287
Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy DOI
Thanh Chung Pham, Nguyễn Văn Nghĩa,

Yeonghwan Choi

и другие.

Chemical Reviews, Год журнала: 2021, Номер 121(21), С. 13454 - 13619

Опубликована: Сен. 28, 2021

This review presents a robust strategy to design photosensitizers (PSs) for various species. Photodynamic therapy (PDT) is photochemical-based treatment approach that involves the use of light combined with light-activated chemical, referred as PS. Attractively, PDT one alternatives conventional cancer due its noninvasive nature, high cure rates, and low side effects. PSs play an important factor in photoinduced reactive oxygen species (ROS) generation. Although concept photosensitizer-based photodynamic has been widely adopted clinical trials bioimaging, until now, our surprise, there no relevant article on rational designs organic PDT. Furthermore, most published articles focused nanomaterials nanotechnology based traditional PSs. Therefore, this aimed at reporting recent strategies develop innovative enhanced therapy, each example described detail instead providing only general overview, typically done previous reviews PDT, provide intuitive, vivid, specific insights readers.

Язык: Английский

Процитировано

1204
Role of GPX4 in ferroptosis and its pharmacological implication DOI

Tobias Seibt,

Bettina Proneth, Marcus Conrad

и другие.

Free Radical Biology and Medicine, Год журнала: 2018, Номер 133, С. 144 - 152

Опубликована: Сен. 13, 2018

Язык: Английский

Процитировано

1160
The development of the concept of ferroptosis DOI
Tal Hirschhorn, Brent R. Stockwell

Free Radical Biology and Medicine, Год журнала: 2018, Номер 133, С. 130 - 143

Опубликована: Сен. 27, 2018

Язык: Английский

Процитировано

880
The chemical basis of ferroptosis DOI
Marcus Conrad, Derek A. Pratt

Nature Chemical Biology, Год журнала: 2019, Номер 15(12), С. 1137 - 1147

Опубликована: Ноя. 18, 2019

Язык: Английский

Процитировано

737
Recent progress of chemodynamic therapy-induced combination cancer therapy DOI
Xianwen Wang,

Xianyan Zhong,

Zhuang Liu

и другие.

Nano Today, Год журнала: 2020, Номер 35, С. 100946 - 100946

Опубликована: Авг. 13, 2020

Язык: Английский

Процитировано

578
All-in-One Theranostic Nanoagent with Enhanced Reactive Oxygen Species Generation and Modulating Tumor Microenvironment Ability for Effective Tumor Eradication DOI
Yang Liu, Wenyao Zhen, Longhai Jin

и другие.

ACS Nano, Год журнала: 2018, Номер 12(5), С. 4886 - 4893

Опубликована: Май 4, 2018

Despite regulation of the reactive oxygen species (ROS) level is an intelligent strategy for cancer therapy, therapeutic effects ROS-mediated therapy (including photodynamic (PDT) and chemodynamic (CDT)) are limited by reliance, inherent flaws traditional photosensitizers, strict reaction conditions effective Fenton reaction. Herein, we reported biocompatible copper ferrite nanospheres (CFNs) with enhanced ROS production under irradiation a 650 nm laser through direct electron transfer photoenhanced high photothermal conversion efficiency upon exposure to 808 laser, exhibiting considerable improved synergistic treatment effect. Importantly, exploiting properties O2 generation glutathione (GSH) depletion CFNs, CFNs relieve hypoxia antioxidant capability tumor, achieving CDT PDT. The relaxivity 468.06 mM–1 s–1 enables act as outstanding contrast agent MRI in vitro vivo. These findings certify potential such "all one" nanotheranostic integrated PDT, CDT, (PTT), imaging capabilities along modulating tumor microenvironment function theranostics cancer.

Язык: Английский

Процитировано

563