Eliminating Aggressive Cancers via PROTAC-like Inducers of Ferroptosis DOI Open Access
Avital Oknin-Vaisman, Deepanjan Panda, Rostislav Novak

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 29, 2024

Abstract Aggressive and therapy-resistant cancers present a significant challenge to treatment are associated with poor patients’ survival. Identifying molecular pathways compounds that target these is critical for improving patient outcomes. RNF4, an E3-ubiquitin ligase, pivotal in oncoprotein stabilization DNA repair, enhancing cancer cell survival driving tumorigenesis. Elevated RNF4 levels prognosis patients. Here, we describe the development of R4VPs, proteolysis-targeted chimeras-like (PROTACs-like). R4VPs promote degradation reduce its stabilized oncoproteins. Notably, induce ferroptotic death selectively cells, sparing non-tumorigenic primary cells. Surprisingly, R4VPs-induced ferroptosis independent but preferentially targets tumor-driving mutations, particularly those EGFR pathway, while not affecting PI3K-transformed effectively melanoma sarcomas including patient-derived sarcoma tumor Our findings highlight potential inducers such as therapeutic strategy therapy resistance, aggressive, hard-to-treat cancers. Teaser cells non-transomed

Язык: Английский

Exploring the Mechanism of Ferroptosis Induction by Sappanone A in Cancer: Insights into the Mitochondrial Dysfunction Mediated by NRF2/xCT/GPX4 Axis DOI Creative Commons

Junyan Wang,

Haowen Zhuang,

Xiaocui Yang

и другие.

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(13), С. 5145 - 5161

Опубликована: Янв. 1, 2024

Non-small cell lung cancer (NSCLC), a major subtype of cancer, encompasses squamous carcinoma, adenocarcinoma, and large carcinoma. Compared to small NSCLC cells grow divide more slowly, their metastasis occurs at later stage. Currently, chemotherapy is the primary treatment for this disease. Sappanone A (SA) flavonoid compound extracted from plant Caesalpinia sappan, known its antitumor, redox-regulating, anti-inflammatory properties. Recent studies have investigated interaction SA with mitochondrial pathways in regulating death through Nrf-2/GPX-4/xCT axis. This study specifically explores mechanism by which affects morphology structure regulation mitophagy biogenesis tumor cells. The primarily utilizes second-generation transcriptomic sequencing data molecular docking techniques elucidate role programmed omics results indicate that significantly targets genes involved oxidative phosphorylation, mitophagy, dynamics, stress. Further findings confirmed Nrf-2/GPX4/xCT pathway serves as crucial target NSCLC. Knockdown Nrf-2 (si-Nrf-2) overexpression (ad-Nrf-2) were shown modulate therapeutic efficacy varying degrees. Additionally, modifications GPX4/xCT affected regulatory effects on autophagy, biogenesis, energy metabolism. These mechanisms may be mediated caspase ferroptosis-related signaling. Molecular biology experiments demonstrated intervention further inhibits phosphorylation FUNDC1 Tyr18 downregulates TOM20 expression. was found reduce expression PGC1α, Nrf-1, Tfam, resulting decrease respiration Overexpression counteract biogenesis. Confocal microscopy revealed increases fragmentation, subsequently inducing pathway-mediated death. However, genetic modification altered In conclusion, has been identified promising agent apoptosis ferroptosis represent key Targeting axis offers novel approach maintaining homeostasis within cellular microenvironment.

Язык: Английский

Процитировано

13
NFE2L2 and ferroptosis resistance in cancer therapy DOI Open Access
Daolin Tang, Rui Kang

Cancer Drug Resistance, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

NFE2-like basic leucine zipper transcription factor 2 (NFE2L2, also known as NRF2), is a key in the cellular defense against oxidative stress, playing crucial role cancer cell survival and resistance to therapies. This review outlines current knowledge on link between NFE2L2 ferroptosis - form of regulated death characterized by iron-dependent lipid peroxidation within cells. While activation can protect normal cells from damage, its overexpression contributes drug upregulating antioxidant defenses inhibiting ferroptosis. We delve into molecular pathways ferroptosis, highlighting involvement target genes, such

Язык: Английский

Процитировано

6
OSGIN1 promotes ferroptosis resistance by directly enhancing GCLM activity DOI
Yuanyuan Jia, Xinyue Zhang, Yiqing Cai

и другие.

Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 740, С. 151015 - 151015

Опубликована: Ноя. 17, 2024

Язык: Английский

Процитировано

4
Lactate-Fueled Theranostic Nanoplatforms for Enhanced MRI-Guided Ferroptosis Synergistic with Immunotherapy of Hepatocellular Carcinoma DOI
Xiaoxiao Chen, Feng Zhang,

Chenying Lu

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Treatment for hepatocellular carcinoma (HCC) may be improved with ferroptosis, a regulated form of cell death. However, the sensitivity HCC to ferroptosis was strongly limited by lactic acid. In this study, platelet membrane (PM)-engineered nanoparticle loaded erastin, superparamagnetic iron oxide nanoparticles (SPIO) and lactate oxidase (LOX) (termed PM@ESL NPs) designed magnetic resonance imaging (MRI)-guided enhanced ferroptosis-immunotherapy HCC. It found that NPs could actively accumulate into tumor due tumor-homing ability PM. Subsequently, effectively enhance removing acid in tumor. The removal also produces hydrogen peroxide (H2O2), which therefore converted cytotoxic hydroxyl radicals reaction H2O2 Fe2+/Fe3+ released from SPIO. Due combined chemodynamic therapy (CDT), NPS showed strong induce immunogenic death (ICD), suppress growth metastasis when αPD-L1 immunotherapy. Furthermore, incorporation SPIO endows an outstanding MRI-T2 monitoring capability treatment. conclusion, study introduces pioneering MRI-guided approach enhances tumors synergistically improves

Язык: Английский

Процитировано

0
Engineered hybrid exosomes responsive to reactive oxygen species target the treatment of spinal cord injury by repairing mitochondrial damage and promoting neuronal function recovery DOI

Daoyong Li,

Zhanpeng Guo,

Mingyu Bai

и другие.

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160669 - 160669

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Engineering Iridium Nanoclusters for Boosting Ferroptotic Cell Death by Regulating GPX4 and p53 Functions DOI
Xiaoyu Cui, Bin Chen, Ying Chen

и другие.

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Abstract Emerging evidence indicates that modulating glutathione peroxidase 4 (GPX4) to induce ferroptosis is a promising strategy for tumor treatment. However, most of the GPX4 small molecule inhibitors face limitations due their poor delivery efficacy and low specificity activation. Herein, ferroptosis‐inducing nanomedicine developed integrates nutlin‐3 with iridium oxide nanoclusters (NUT‐IrO x NCs) enhanced ferroptosis‐driven multimodal therapeutic in colorectal cancer (CRC). This NUT‐IrO NCs can (GSH) depletion via Ir (VI)‐Ir (III) transition, while nutlin‐3, well‐established inhibitor p53‐MDM2 interaction, suppresses GSH production by modulation p53/SLC7A11/xCT signaling pathway. The reduction intracellular results pronounced reductions enzymatic activity, consequently leading lipid peroxidation accumulation further enhancing ferroptosis‐induced CRC therapy. dual‐pronged approach demonstrates robust anticancer effects favorable biocompatibility both vitro vivo models. study provides an effective highlights benefits inhibiting GSH/GPX4 activating multiple regulatory pathways, providing alternative avenue

Язык: Английский

Процитировано

0
BMAL1-depletion remodels ceramide metabolism to regulate ferroptosis and sorafenib chemosensitivity in acute myeloid leukemia DOI Creative Commons

Hong Zheng,

Zhi Lin, Dan Wang

и другие.

iScience, Год журнала: 2025, Номер 28(4), С. 112054 - 112054

Опубликована: Март 22, 2025

Язык: Английский

Процитировано

0
Glutathione Metabolism in Ferroptosis and Cancer Therapy DOI
Xiangfei Xue, Manyuan Wang,

Jiangtao Cui

и другие.

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217697 - 217697

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Mechanisms and therapeutic target of anti-tumour treatment-related Ferroptosis: How to improve cancer therapy? DOI Open Access
Xiangyu Zhou, Lin Lin

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 179, С. 117323 - 117323

Опубликована: Авг. 28, 2024

Recently, increased attention has been focused on the regulatory mechanism and potential clinical application of ferroptosis in cancer cells, especially therapy-related ferroptosis. However, treatment-related prospects strategies for future treatment still require further clarification. This review highlights molecular relationships between different antitumour drugs, including commonly used chemotherapy radiation therapy vitamins, also proposes treatments that involve ferroptosis, with an aim to develop a new strategy transformative emerging field improve therapy.

Язык: Английский

Процитировано

2
β-Elemene promotes ferroptosis and reverses radioresistance in gastric cancer by inhibiting the OTUB1-GPX4 interaction DOI Creative Commons

Jiancheng He,

Ming Li,

Jiapeng Bao

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Окт. 17, 2024

β-Elemene, derived from

Процитировано

2