Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Авг. 16, 2024

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.

Язык: Английский

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A comprehensive review on doxorubicin: mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer

Drug Delivery and Translational Research, Год журнала: 2024, Номер unknown

Опубликована: Июнь 17, 2024

Язык: Английский

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Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing

Cancers, Год журнала: 2024, Номер 16(8), С. 1463 - 1463

Опубликована: Апрель 11, 2024

Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements comprehending the disease, cancer remains leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence drug resistance further complicates therapeutic efficacy, underscoring urgent need for alternative approaches. Drug repurposing, characterized by utilization existing drugs novel clinical applications, emerges promising avenue addressing these challenges. Repurposed drugs, comprising FDA-approved (in other disease indications), generic, off-patent, failed medications, offer distinct advantages including established safety profiles, cost-effectiveness, expedited development timelines compared to discovery processes. Various methodologies, such knowledge-based analyses, drug-centric strategies, computational approaches, play pivotal roles identifying potential candidates repurposing. However, despite promise repurposed repositioning confronts formidable obstacles. Patenting issues, financial constraints associated with conducting extensive trials, necessity combination therapies overcome limitations monotherapy pose This review provides an in-depth exploration covering diverse array approaches experimental, re-engineering protein, nanotechnology, methods. Each avenues presents opportunities obstacles pursuit uses drugs. By examining multifaceted landscape this aims comprehensive insights into its transform therapeutics.

Язык: Английский

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Buthionine sulfoximine acts synergistically with doxorubicin as a sensitizer molecule on different tumor cell lines

Journal of Toxicology and Environmental Health, Год журнала: 2025, Номер unknown, С. 1 - 23

Опубликована: Янв. 15, 2025

The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, clinical use is limited due side effects, including cardiotoxicity, myelosuppression, and resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse potentially reducing the required dose while maintaining efficacy. aim of present study was examine effects different concentrations BSO DOX, both individually combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 sarcoma), SVEC4–10 endothelial) cell lines. Cell viability, migration, clonogenicity were assessed using following assays MTT, scratch, colony formation. Antioxidant levels GSH, as well activities catalase (CAT), superoxide dismutase (SOD) measured. alone exhibited minimal cytotoxic reduced viability significantly. combination BSO+DOX decreased IC50 values most lines, demonstrating synergistic effect, especially B16/F10, S180, cells. significantly inhibited migration compared alone. While GSH treatment CAT SOD increased administration but remained unchanged by BSO. These suggest that may be considered valuable tool improve therapeutic efficacy, particularly cases chemotherapy-resistant tumors, enhances activity systemic toxicity.

Язык: Английский

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Remote Co-Loading of Doxorubicin and Hydralazine into PEGylated Liposomes: In Vitro Anti-Proliferative Effect Against Breast Cancer

Molecules, Год журнала: 2025, Номер 30(7), С. 1549 - 1549

Опубликована: Март 31, 2025

Doxorubicin (DOX), an anthracycline chemotherapeutic agent, demonstrates efficacy against various types of cancer. Combining DOX with the antihypertensive drug hydralazine (HDZ) has been proposed as cardioprotective combination therapy, allowing for use a reduced dose. The current study describes remote co-loading and HDZ into PEGylated liposomes using, first time, simultaneous pH gradient technique. First, were prepared using ethanol injection method remotely loaded HDZ. Then, DOX- HDZ-loaded (Lip-DOX-HDZ) characterized DLS, TEM, FTIR, thermal analysis, leakage, stability. Furthermore, cellular uptake cytotoxicity evaluated in two human breast cancer cell lines (MCF7 MDA-MB-231) normal (human dermal fibroblasts (HDFs) rat cardiac cells (H9C2)). results revealed that Lip-DOX-HDZ had particle size 158 ± 18 nm, PDI 0.22 0.08, zeta potential −22 5 mV. encapsulation efficiency was 90% 30%, respectively. Moreover, IC50 values showed higher MDA-MB-231 (5.5 0.4 µM) MCF7 (6.25 0.9 compared to cells: HDF (20 3.0 H9C2 (19.37 2.0 µM). Our found ~4-fold lower toxicity selectivity (HDFs H9C2), cells. This suggests is promising nanocarrier both HDZ, clinically potent molecules.

Язык: Английский

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Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 10, 2025

Breast cancer is the most commonly diagnosed worldwide. Metal metabolism pivotal for regulating cell fate and drug sensitivity in breast cancer. Iron copper are essential metal ions critical maintaining cellular function. The accumulation of iron triggers distinct death pathways, known as ferroptosis cuproptosis, respectively. Ferroptosis characterized by iron-dependent lipid peroxidation, while cuproptosis involves copper-induced oxidative stress. They increasingly recognized promising targets development anticancer drugs. Recently, compelling evidence demonstrated that interplay between plays a crucial role progression. This review elucidates converging pathways Moreover, we examined value genes associated with clinical diagnosis treatment cancer, mainly outlining potential co-targeting approach. Lastly, delve into current challenges limitations this strategy. In general, offers an overview interaction offering valuable perspectives further research treatment.

Язык: Английский

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Formation and evaluation of doxorubicin and cromoglycate metal–organic framework for anti-cancer activity

Nanomedicine, Год журнала: 2025, Номер unknown, С. 1 - 13

Опубликована: Янв. 31, 2025

We develop and evaluate copper-based metal-organic frameworks (Cu-MOFs) incorporating cromolyn as a linker to enhance structural stability, drug delivery efficiency, therapeutic potential, particularly for breast cancer treatment. Two Cu-MOF formulations were synthesized: Cu-MOFs-BDC-DOX (using terephthalic acid) Cu-MOFs-CROMO-DOX linker). Characterization was performed using SEM/TEM morphology, FTIR, XRD, TGA confirm integrity. Drug encapsulation efficiency release profiles assessed, followed by in vitro cytotoxicity, cell migration, colony formation assays MDA-MB-231 cells. Both demonstrated high (83-91%) sustained over 48 h at pH 7.4. exhibited superior cytotoxicity with an IC50 of 0.88 ± 0.07 µM compared 7.1 0.11 Cu-MOFs-BDC-DOX. inhibit migration dose-dependent manner. The formulation enhanced outperforming its counterpart targeting This study highlights the promise MOF-based nanocarriers overcoming limitations conventional chemotherapy, offering pathway more effective targeted treatments reduced side effects.

Язык: Английский

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Metal–organic frameworks as nanoplatforms for combination therapy in cancer treatment

Medical Oncology, Год журнала: 2024, Номер 42(1)

Опубликована: Дек. 9, 2024

Язык: Английский

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Pharmacokinetics–Pharmacodynamics Modeling for Evaluating Drug–Drug Interactions in Polypharmacy: Development and Challenges

Clinical Pharmacokinetics, Год журнала: 2024, Номер 63(7), С. 919 - 944

Опубликована: Июнь 18, 2024

Язык: Английский

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Hydralazine and Hydrazine Derivatives: Properties, Applications, and Repositioning Potential

Chemistry & Biodiversity, Год журнала: 2024, Номер unknown

Опубликована: Окт. 21, 2024

The investigation of new drugs is slow and costly. Drug repositioning, like with Hydralazine (HDZ), an old antihypertensive, can accelerate the process. HDZ its hydrazonic derivatives exhibit diverse biological activities, promising for drugs. This review explores HDZ's repositioning potential derivatives' applications in various activities. It identified 70 relevant articles through database searches. shows neurology, oncology, nephrology, gynecology, clinical trials up to Phase III. Hydralazine-valproate, marketed Mexico, proves effective combination chemotherapy. Hydrazonic offer broad medicine. Studying their structure-activity relationship enhance efficacy. summarizes properties pharmacological activities succinctly.

Язык: Английский

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