Cancer-associated fibroblasts promote doxorubicin resistance in triple-negative breast cancer through enhancing ZFP64 histone lactylation to regulate ferroptosis DOI Creative Commons
Kejing Zhang, Lei Guo, Xin Li

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 28, 2025

Cancer-associated fibroblasts (CAFs) have been identified to drive chemotherapy resistance in triple-negative breast cancer (TNBC). This study evaluated the functions of CAFs-mediated suppressive ferroptosis doxorubicin (DOX) TNBC and its detailed molecular mechanisms. cell lines were co-cultured with CAFs isolated from DOX-sensitive (CAF/S) or DOX-resistant (CAF/R) tissues. Cell viability death assessed by counting Kit-8 (CCK-8) propidium iodide (PI) staining. Ferroptosis was detection Fe2+, malondialdehyde (MDA), glutathione (GSH), lipid reactive oxygen species (ROS) levels. Histone lactylation determined lactate production, pan-Kla H3K18la expression. Molecular mechanism chromatin immunoprecipitation (ChIP) dual luciferase reporter system. Molecule protein expression detected quantitative Real-Time PCR (RT-qPCR), Western blotting, immunofluorescence immunohistochemical cells injected into mammary fat pad nude mice investigate DOX sensitivity vivo. CAFs-derived repressed confer DOX. Moreover, zinc finger 64 (ZFP64) elevated associated high histone level. facilitated enhance ZFP64 expression, which triggered inhibition resistance. In addition, bound promoters GTP cyclohydrolase-1 (GCH1) ferritin heavy chain 1 (FTH1), thereby promoting their Rescue experiments indicated that silencing-induced could be counteracted GCH1 FTH1 overexpression. acted as a inhibitor cause via lactylation-mediated up-regulation subsequent promotion GCH1-induced peroxidation FTH1-induced intracellular Fe2+ consumption.

Язык: Английский

Ferroptosis-related signaling pathways in cancer drug resistance DOI Open Access
Yang Yang‐Hartwich,

Simin Yu,

Wanyao Liu

и другие.

Cancer Drug Resistance, Год журнала: 2025, Номер 8(1)

Опубликована: Янв. 6, 2025

Ferroptosis is an iron-dependent form of programmed cell death induced by lipid peroxidation. This process regulated signaling pathways associated with redox balance, iron metabolism, and metabolism. Cancer cells' increased demand makes them especially susceptible to ferroptosis, significantly influencing cancer development, therapeutic response, metastasis. Recent findings indicate that cells can evade ferroptosis downregulating key related this process, contributing drug resistance. underscores the possibility modulating as approach counteract resistance enhance efficacy. review outlines involved in their interactions cancer-related pathways. We also highlight current understanding resistance, offering insights into how targeting provide novel approaches for drug-resistant cancers. Finally, we explore potential ferroptosis-inducing compounds examine challenges opportunities development evolving field.

Язык: Английский

Процитировано

1
Targeting Protein Arginine Methyltransferases in Breast Cancer: Promising Strategies DOI

Yuancheng Wei,

Xiaodan Lyu,

Wang Jia

и другие.

European Journal of Pharmacology, Год журнала: 2025, Номер 992, С. 177350 - 177350

Опубликована: Фев. 4, 2025

Язык: Английский

Процитировано

1
Ferroptosis induction via targeting metabolic alterations in triple-negative breast cancer DOI Open Access
Yaru Wang,

Yue Sun,

Feiran Wang

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 169, С. 115866 - 115866

Опубликована: Ноя. 10, 2023

Triple-negative breast cancer (TNBC), the most aggressive form of cancer, presents severe threats to women's health. Therefore, it is critical find novel treatment approaches. Ferroptosis, a newly identified programmed cell death, marked by buildup lipid reactive oxygen species (ROS) and high iron concentrations. According previous studies, ferroptosis sensitivity can be controlled number metabolic events in cells, such as amino acid metabolism, metabolism. Given that TNBC tumors are rich lipids, inducing these potential approach for treatment. Notably, adaptability cells allows them coordinate an attack on one or more pathways initiate ferroptosis, offering perspective improve drug resistance clinical therapy TNBC. However, clear picture still needs completely revealed. In this review, we provide overview recent advancements regarding connection between acid, iron, metabolism We also discuss probable significance innovative target chemotherapy, radiotherapy, immunotherapy, nanotherapy natural product TNBC, highlighting its therapeutic application prospects.

Язык: Английский

Процитировано

16
Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma DOI Creative Commons
Haiqiu Li,

Yichen Dou,

Hang Yang

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Март 10, 2024

Abstract Background Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), lack efficient inducers poor solubility photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination cancers. Results Herein, an ferroptosis/PDT integrated nanoplatform is constructed based on chlorin e6-modified Fe ions-doped (Fe-CDs@Ce6). As a novel type iron-carbon hybrid nanoparticles, as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis inhibit migration mouse skin cells (B16), but have no toxicity normal cells. The nano-conjugated structures facilitate not only aqueous dispersibility Ce6, also self-accumulation ability Fe-CDs@Ce6 within area without requiring extra targets. Moreover, therapeutic effects synergistically enhanced due increased GSH depletion by PDT elevated singlet oxygen ( 1 O 2 ) production efficiency Fe-CDs. When combined with laser irradiation, tumor growth be significantly suppressed through cyclic administration. T -weighted magnetic resonance imaging (MRI) capability reveals potentials cancer diagnosis navigation therapy. Conclusions Our findings indicate multifunctionality in effectively combining therapy, targeting MRI imaging, which enables become promising biocompatible treatment melanoma. Graphic

Язык: Английский

Процитировано

6
Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer DOI Creative Commons

Yaxun Guo,

Yuzhan Li, Zhongmei Zhou

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Ноя. 30, 2024

Abstract Background Triple-negative breast cancer (TNBC) is currently the most aggressive subtype of cancer, characterized by high heterogeneity and strong invasiveness, lacks effective therapies. PRMT5, a type II protein arginine methyltransferase, upregulated in numerous cancers, including TNBC, plays critical role, marked it as an attractive therapeutic target. PROTAC (Proteolysis Targeting Chimeras) innovative drug development technology that utilizes ubiquitin-proteasome system (UPS) to degrade target proteins, which higher activity, enhanced safety, lower resistance, reduced toxicity, offering significant value for clinical translation. Methods This study develop potential degraders targeting PRMT5 vitro vivo. Results Through design, synthesis screening series targeted compounds, we identified YZ-836P compound exerted cytotoxic effects levels its key downstream KLF5 TNBC after 48 h. Its efficacy was significantly superior had been reported. induced G1 phase cell cycle arrest apoptosis cells. Additionally, demonstrated promoted ubiquitination degradation cereblon (CRBN)-dependent manner. Notably, exhibited pronounced inhibiting growth patient-derived organoids xenografts nude mice. Conclusions These findings position promising candidate advancing treatment modalities TNBC. Trial registration Ethics Committee Yunnan Cancer Hospital, KYCS2023-078. Registered 7 June 2023.

Язык: Английский

Процитировано

6
Ferroptosis: Molecular perspective, cellular influence, cancer manifestation, and therapeutic potentials DOI
Pawan Kumar Pandey,

Saurabh Bhorkade,

Shikha Jha

и другие.

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 100, С. 105998 - 105998

Опубликована: Июль 31, 2024

Язык: Английский

Процитировано

5
MTA-cooperative PRMT5 inhibitors enhance T cell-mediated antitumor activity in MTAP-loss tumors DOI Creative Commons
Si Chen, Jiakai Hou, Roshni Jaffery

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(9), С. e009600 - e009600

Опубликована: Сен. 1, 2024

Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression activity impairs effector functions cells. Here, we sought identify strategies specifically inhibit tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for treatment, particularly methylthioadenosine phosphorylase (MTAP)-loss cancer.

Язык: Английский

Процитировано

5
Identification of PRMT5 as a therapeutic target in cholangiocarcinoma DOI

Jasmin Elurbide,

Leticia Colyn, María U. Latasa

и другие.

Gut, Год журнала: 2024, Номер 74(1), С. 116 - 127

Опубликована: Сен. 11, 2024

Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors limited. Therefore, new therapeutic strategies need be identified.

Язык: Английский

Процитировано

4
Targeting NQO1 induces ferroptosis and triggers anti-tumor immunity in immunotherapy-resistant KEAP1-deficient cancers DOI
Zhennan Yuan, Yuqin Wang,

Boyu Qin

и другие.

Drug Resistance Updates, Год журнала: 2024, Номер 77, С. 101160 - 101160

Опубликована: Окт. 17, 2024

Язык: Английский

Процитировано

4
The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy DOI Creative Commons
Zhiguo Mao, Yilong Hu,

Yinan Zhao

и другие.

APOPTOSIS, Год журнала: 2024, Номер unknown

Опубликована: Июнь 9, 2024

Abstract Ferroptosis is a form of cell death that triggered by the presence ferrous ions and characterized lipid peroxidation induced these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, necrosis. A notable aspect ferroptosis its ability inhibit uncontrolled tumor replication immortalization, especially in malignant, drug-resistant, metastatic tumors. Additionally, immunotherapy, novel therapeutic approach for tumors, has been found have reciprocal regulatory relationship with context anti-tumor therapy. comprehensive analysis immunotherapy therapy presented this paper, highlighting potential mutual adjuvant effects. Specifically, we discuss mechanisms underlying emphasizing their improve immune microenvironment enhance immunotherapeutic Furthermore, investigate how factors may increase sensitivity cells ferroptosis. We aim provide prospective view promising value combined anticancer elucidating network between each. Graphical involves intricate crosstalk cells. Through MHC recognition, CD8 + T activate JAK1/STAT1 pathway cells, impairing function System Xc reducing GSH GPX4 expression promote activation STAT1-IRF1-ACSL4 could also blockade antioxidant induces ferroptosis, released DAMPs DCs maturation through cGAMP-STING-TBK1 pathway, leading antigen presentation activates release M1-type polarization macrophages, which exerts an effect. effects be enhanced blocking inhibitory checkpoints such as PD-1, PD-L1, CTLA4, LAG3. Abbreviations: ACSL4, acyl-CoA synthetase long-chain family member 4; BH4, tetrahydrobiopterin; cGAMP, cyclic GMP-AMP; cytotoxic lymphocyte-associated antigen-4; DCs, dendritic cells; DHFR, dihydrofolate reductase; DHODH, dihydroorotate dehydrogenase; GPX4, glutathione peroxidase GSH, glutathione; HIF-1α, Hypoxia-Inducible Factor-1α;IFN-γ, interferon-γ; IRF1, interferon factor 1;IRP1, iron protein 1; JAK 1, janus kinase; LAG3, lymphocyte gene 3; MHC, major histocompatibility complex; NRF2, nuclear erythroid-2-related 2; programmed -1; ligand PUFA, polyunsaturated fatty acid; ROS, reative oxygen species; STAT1, signal transducer activator transcription STING, stimulator genes; TBK1, TANK-binding kinase 1 TLR2, toll-like receptor 2. This diagram was drawn Figdraw ( www.figdraw.com ).

Язык: Английский

Процитировано

3