Targeting necroptosis in MCF-7 breast cancer cells: In Silico insights into 8,12-dimethoxysanguinarine from Eomecon Chionantha through molecular docking, dynamics, DFT, and MEP studies

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0313094 - e0313094

Опубликована: Янв. 7, 2025

Breast cancer remains a significant challenge in oncology, highlighting the need for alternative therapeutic strategies that target necroptosis to overcome resistance conventional therapies. Recent investigations into natural compounds have identified 8,12-dimethoxysanguinarine (SG-A) from Eomecon chionantha as potential inducer. This study presents first computational exploration of SG-A interactions with key necroptotic proteins—RIPK1, RIPK3, and MLKL—through molecular docking, dynamics (MD), density functional theory (DFT), electrostatic (MEP) analyses. Molecular docking revealed exhibited stronger affinity MLKL (-9.40 kcal/mol) compared co-crystallized ligand (-6.29 kcal/mol), while its RIPK1 (-6.37 RIPK3 (-7.01 was lower. MD simulations further demonstrated stability within site, RMSD values stabilizing between 1.4 3.3 Å over 300 ns, indicating consistent interaction pattern. RMSF analysis indicated preservation protein backbone flexibility, average fluctuations under 1.7 Å. The radius gyration (Rg) results value ~15.3 across systems, confirming role maintaining integrity. Notably, maintains two critical H-bonds active site MLKL, reinforcing interaction. Principal component (PCA) reduction MLKL’s conformational space upon binding, implying enhanced stabilization. Dynamic cross-correlation map (DCCM) induced highly correlated motions, reducing internal ligand. MM-PBSA binding efficacy SG-A, free energy -31.03 ± 0.16 kcal/mol against surpassing control (23.96 0.11 kcal/mol). In addition, individual residue contribution highlighted interactions, ARG149 showing (-176.24 MLKL-SG-A complex. DFT MEP studies corroborated these findings, revealing electronic structure is conducive stable characterized by narrow band gap (~0.16 units) distinct favourable induction. conclusion, has emerged compelling inducer breast therapy, warranting experimental validation fully realize potential.

Язык: Английский

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CD44 variant exons induce chemoresistance by modulating cell death pathways

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 6, 2025

Cancer chemoresistance presents a challenge in oncology, often leading to treatment failure and disease progression. CD44, multifunctional cell surface glycoprotein, has garnered attention for its involvement various aspects of cancer biology. Through alternative splicing, CD44 can form isoforms with the inclusion only standard exons, typical normal tissue, or addition variant frequently expressed tissue associated chemoresistance. The functions involved regulation signaling pathways are being actively studied, significance specific exons modulating death pathways, central response cells chemotherapy, begins become apparent. This review provides comprehensive analysis association exons/total clinical outcomes patients undergoing chemotherapy. role v6, v9 others significant effect on patient chemotherapy by means key cellular such as apoptosis, ferroptosis autophagy modulation is further identified, their impact drug resistance highlighted. An overview trials aimed at targeting exon-containing provided, possible directions development CD44-targeted therapeutic strategies discussed.

Язык: Английский

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Genomic Landscape of Breast Cancer: Study Across Diverse Ethnic Groups

Diseases, Год журнала: 2025, Номер 13(3), С. 86 - 86

Опубликована: Март 17, 2025

Background: Breast cancer (BC) is the most common among women worldwide, with incidence and mortality rates varying across ethnic groups due to sociodemographic, clinicopathological, genomic differences. This study aimed characterize landscape of BC in diverse using computational tools explore these variations. Methodology: cBioPortal was used analyze genomic, sociodemographic data from 1084 samples. Mutated genes were classified based on GeneCards platform data. Enrichment analysis performed CancerHallmarks, not found compared MSigDB’s Hallmark Gene Sets. Genes absent both further analyzed NDEx through Cytoscape.org their role cancer. Results: Significant differences (p < 0.05) observed sex, tumor subtypes, genetic ancestry, median fraction altered genome, mutation count, frequencies groups. We identified frequently mutated genes. Some be associated classic hallmarks, such as replicative immortality, sustained proliferative signaling, evasion growth suppressors. However, exact some remains unclear, highlighting need for research better understand involvement biology. Conclusions: significant clinicopathological variations While key hallmarks found, incomplete characterization highlights research, especially focusing groups, biology improve personalized treatments.

Язык: Английский

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Artemetin Inhibits Cell Growth and Activates Caspase-dependent Apoptotic Cell Death Colon Cancer HCT-116 Cells

Pharmacognosy Magazine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Background Colon cancer, a prevalent form of gastrointestinal malignancy, poses significant public health issue globally. The onset colon cancer is complex mechanism implicating genetic and environmental factors, including dietary habits lifestyle choices. Purpose current study was undertaken to investigate the anti-tumor effects artemetin against cells. Materials Methods influence on proliferation HCT-116 cells evaluated with an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) test. Also, extent apoptosis in both untreated artemetin-exposed studied using dual staining technique. activities caspase enzymes (caspase-3, -8, -9) were commercial diagnostic kit. Results administration several dosages significantly suppressed dose-dependently. Furthermore, treatment induced cells, which evidenced by assay. Artemetin also elevated caspase-3, -9 Conclusion present revealed that possesses anti-cancer reducing cell viability inducing caspase-mediated Consequently, findings indicate as favorable candidate for future therapy.

Язык: Английский

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Copper and Colorectal Cancer

Cancers, Год журнала: 2024, Номер 16(21), С. 3691 - 3691

Опубликована: Окт. 31, 2024

Minerals constitute only 5% of the typical human diet but are vital for health and functionality. Copper, a trace element, is absorbed by gut at 30-40% from diets industrialized countries. The liver produces metallothioneins, which store copper. Copper crucial mitochondrial respiration, pigmentation, iron transport, antioxidant defense, hormone production, extracellular matrix biosynthesis. deficiency, often caused mutations in

Язык: Английский

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Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Ноя. 15, 2024

Cancer is a complex disease characterized by specific “mission-critical” events that drive the uncontrolled growth and spread of tumor cells their offspring. These are essential for advancement disease. One main contributors to these dysregulation cell death pathways—such as apoptosis, necroptosis, ferroptosis, autophagy, pyroptosis, cuproptosis, parthanatos and—allows cancer avoid programmed continue proliferating unabated. The different pathways in cancers provide useful targets treatment. This review examines recent progresses preclinical clinical development targeting dysregulated To develop effective therapies, it identify target mission-critical prevent from timely death. By precisely crucial events, researchers can therapies with maximum impact minimal side effects. A comprehensive understanding molecular cellular mechanisms underlying regulated will further highly personalized treatments.

Язык: Английский

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Excavating regulated cell death signatures to predict prognosis, tumor microenvironment and therapeutic response in HR+/HER2- breast cancer

Translational Oncology, Год журнала: 2024, Номер 50, С. 102117 - 102117

Опубликована: Сен. 6, 2024

Язык: Английский

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