Identifying the Effects of Montelukast in Head and Neck Cancer Cells

Dicle Medical Journal / Dicle Tip Dergisi, Journal Year: 2025, Volume and Issue: 52(1), P. 87 - 94

Published: March 13, 2025

Objective: Head and neck squamous cell carcinoma (HNSCCs) are one of the most common cancer types worldwide. There different treatment approaches including drug repurposing against HNSCCs. In this study, we aim to evaluate montelukast effect on HNSCC lines by proliferative capacity, self-renewal potential, cycle dynamics. Methods: UM-SCC-47 HSC-3 were cultured treated with 10 uM montelukast. Control cells investigated colony formation assay, sphere assay. Stemness-related markers detected via qRT-PCR analysis was performed flow cytometry. Results: The assay demonstrated that group smaller organized compared control. NANOG SOX2 mRNA levels reduced whereas KLF4 OCT3/4 increased. Colony in group. Cell arrested S phase montelukast-treated groups. Conclusion: Montelukast at a concentration μM impacted several functional properties head cells, highlighting its potential effects context. Future studies should explore broader range concentrations better understand therapeutic dose-dependent effects.

Language: Английский

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Understanding the Role of Bacterial Biofilm in Antibiotic Resistance: Defensive Strategies and Clinical Challenges

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Bacterial biofilms significantly cause persistent exacerbation of infections in the clinical setting. These groups microorganisms are highly resistant to host immune responses and conventional antibiotic therapies, whereas they embedded an extracellular matrix. This chapter provides more detailed information on mechanism biofilm formation involving key stages adherence, maturation, spread, including composition structure a further explores how contribute resistance, physical barriers drug penetration, quorum sensing mechanisms, adaptive resistance strategies such as genetic adaptation, stress responses, persister cells. The role horizontal gene transfer spread within communities is also discussed. discusses challenges posed by biofilm-associated infections, focusing diagnosing treating chronic recurrent factors persistence, limitations current therapeutic options. Finally, we address emerging countermeasures counter mediated biofilms, enzymatic nanomedicine technologies, natural product-based inhibitors, inhibitory agents, photodynamic sonodynamic antimicrobial therapy, combinatorial therapies.

Language: Английский

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Polypharmacology: new drugs in 2023–2024

Pharmacological Reports, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

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Nanohydrogel of Curcumin/Berberine Co‐Crystals Induces Apoptosis via Dual Covalent/Noncovalent Inhibition of Caspases in Endometrial Cancer Cell Lines: The Synergy Between Pharmacokinetics and Pharmacodynamics

Journal of Molecular Recognition, Journal Year: 2025, Volume and Issue: 38(2)

Published: March 1, 2025

ABSTRACT Endometrial cancer remains a significant therapeutic challenge due to drug resistance and heterogeneity. This study leverages the synergistic potential of curcumin (CUR) berberine (BBR) co‐crystals encapsulated in nanohydrogel address these challenges through pharmacokinetically pharmacodynamically targeted strategy. The formulation significantly improves solubility, stability, bioavailability CUR/BBR co‐crystals, optimizing their delivery sustained release under physiological tumor microenvironment conditions. On other hand, dual inhibitory mechanism CUR BBR, with covalently binding active site caspase‐3 BBR non‐covalently targeting allosteric site, achieves enhanced apoptotic activity by disrupting both catalytic conformational functions caspase‐3. In vitro cytotoxicity assays demonstrate remarkable efficacy nanohydrogel, achieving an IC50 12.36 μg/mL against HEC‐59 endometrial cells, outperforming individual components standard Camptothecin (IC50: 17.27 μg/mL). Caspase‐3/7 confirm apoptosis induction for compared alone Camptothecin. Molecular dynamics simulations free energy analyses further validate interaction mode. introduces novel approach enhancing mechanisms, demonstrating CUR‐BBR as robust therapy EC. strategy offers promising platform addressing improving outcomes therapy.

Language: Английский

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Exploring Multi-Target Therapeutic Strategies for Glioblastoma via Endogenous Network Modeling

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3283 - 3283

Published: April 1, 2025

Medical treatment of glioblastoma presents a significant challenge. A conventional medication has limited effectiveness, and single-target therapy is usually effective only in the early stage treatment. Recently, there been increasing focus on multi-target therapies, but vast range possible combinations makes clinical experimentation implementation difficult. From perspective systems biology, this study conducted simulations for based dynamic analysis previously established endogenous networks, validated with single-cell RNA sequencing data. Several potentially target were identified. The findings also highlight necessity rather than intervention strategies cancer treatment, as well promise applications personalized therapies.

Language: Английский

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Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: April 2, 2025

Steroidal compounds have emerged as effective therapeutic agents in oncology. Beyond natural-occurring and synthetic steroids that act cytotoxic anti-tumoral agents, steroidal derivatives can be designed to mime the endogenous substrates of key metabolic enzymes steroidogenesis, thus reducing circulating levels relevant oestrogenic androgenic hormones responsible for cancer survival proliferation. Therefore, enzyme inhibition represents an intriguing endocrine approach treatment hormone-dependent tumours, such breast prostate cancer, with well-known approved drugs several pre-clinical clinical candidates under investigation. This review summarises advancements over past decade (2014-2024) development inhibitors endowed anticancer activity, illustrating their mechanisms action, potential, drug design approaches, current applications. Furthermore, we discuss challenges related resistance, off-target effects, future strategies optimise efficacy

Language: Английский

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Discovery of a novel 4-pyridyl SLC-0111 analog targeting tumor-associated carbonic anhydrase isoform IX through tail-based design approach with potent anticancer activity

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: April 4, 2025

Introduction: Carbonic anhydrase IX (CA IX) is a tumor-associated enzyme involved in cancer progression and survival. Targeting CA with selective inhibitors like SLC-0111 has shown therapeutic potential. This study aimed to develop novel 4-pyridyl analog ( Pyr ) of enhanced anticancer activity. Methods: was synthesized using tail-based design characterized by NMR. Its cytotoxicity tested against normal cell lines. inhibition, cycle effects, apoptosis induction, protein expression changes were evaluated. Molecular docking ADMET predictions assessed binding drug-like properties. Results Discussion: showed toward cells potent inhibition. It induced G0/G1 arrest, apoptosis, modulated p53, Bax, Bcl-2 levels. Docking confirmed strong binding, analysis indicated good oral bioavailability. These results support as promising candidate.

Language: Английский

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Epigenetic Rewiring of Protein Kinase Signalling in T-Cell Acute Lymphoblastic Leukaemia

Kinases and Phosphatases, Journal Year: 2025, Volume and Issue: 3(2), P. 7 - 7

Published: April 12, 2025

T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive neoplastic malignancy characterised by the accumulation of multiple oncogenic and epigenetic alterations in haematopoietic precursors leading to their uncontrolled proliferation bone marrow. For many years it has been established that occurrence activating mutations, transcription factors expression, impairment cell cycle regulators, hyperactivation NOTCH1 signalling play prominent roles pathogenesis this disease. Recently, introduction high-resolution screening next-generation sequencing platforms revealed progenitors accumulate additional affecting protein kinase signalling, translation, control mechanisms, providing novel attractive targets for therapy. While contributions direct genomic events are well understood as causative agents hyperactive pathways, rewiring cascades via DNA methylation, histone post-translational modifications, non-coding miRNAs remains less explored. In review, we provide perspectives on regulatory aspects heterogeneity T-ALL therapeutic outcomes.

Language: Английский

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Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 25, 2024

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These serve competitive endogenous (ceRNAs) through sponging microRNAs regulating expression targeted genes. Moreover, they also directly bind to RNA-binding proteins, can be integrated into complex mechanistic network. E2F1, an extensively studied transcription factor, mediates multiple behaviors by cell cycle progression, metastasis, therapeutic response. Emerging evidence suggests play pivotal role in E2F1 pathway. This review aims elucidate intricate gene regulatory programs between cancer We elaborate distinct networks involved emphasizing potential lncRNAs/E2F1 axes promising targets for therapy. Additionally, we provide novel perspectives current evidence, limitations, future directions targeting human cancers. Fully deciphering network lncRNA/E2F1-mediated mechanisms could facilitate translation findings clinical course, such efforts ultimately significantly improve prognosis patients.

Language: Английский

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Developing a Semi-Supervised Approach Using a PU-Learning-Based Data Augmentation Strategy for Multitarget Drug Discovery

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8239 - 8239

Published: July 28, 2024

Multifactorial diseases demand therapeutics that can modulate multiple targets for enhanced safety and efficacy, yet the clinical approval of multitarget drugs remains rare. The integration machine learning (ML) deep (DL) in drug discovery has revolutionized virtual screening. This study investigates synergy between ML/DL methodologies, molecular representations, data augmentation strategies. Notably, we found SVM match or even surpass performance state-of-the-art DL methods. However, conventional often involves a trade-off true positive rate false rate. To address this, introduce Negative-Augmented PU-bagging (NAPU-bagging) SVM, novel semi-supervised framework. By leveraging ensemble classifiers trained on resampled bags containing positive, negative, unlabeled data, our approach is capable managing rates while maintaining high recall rates. We applied this method to identification multitarget-directed ligands (MTDLs), where are critical compiling list interaction candidate compounds. Case studies demonstrate NAPU-bagging identify structurally MTDL hits ALK-EGFR with favorable docking scores binding modes, as well pan-agonists dopamine receptors. methodology should serve promising avenue screening, especially MTDLs.

Language: Английский

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