Toxicology and Environmental Health Sciences, Год журнала: 2024, Номер unknown
Опубликована: Дек. 26, 2024
Язык: Английский
Cancer Biology & Therapy, Год журнала: 2024, Номер 25(1)
Опубликована: Май 13, 2024
Cervical cancer (CC) is a prevalent malignancy among women worldwide. This study was designed to investigate the role of METTL14 in sorafenib-induced ferroptosis CC. expression and m6A methylation were determined CC tissues, followed by analyzes correlating these factors with clinical features. Subsequently, knocked down cell lines, effects on proliferation, mitochondrial morphology assessed using CCK-8, microscopy, markers associated ferroptosis, respectively. The regulatory relationship between FTH1 verified qRT-PCR luciferase reporter assays. functional significance this interaction further investigated both vitro vivo co-transfecting cells overexpression vectors or shRNAs targeting after sorafenib treatment. significantly reduced lower levels poorer patients' prognosis. Notably, increased during knockdown attenuated ferroptotic response induced cells. identified as direct target METTL14, leading mRNA, resulting stability Furthermore, treatment LY294002 partially counteracted promotion METTL14. In xenograft experiments demonstrated that inhibiting anticancer sorafenib, whereas suppression enhanced its efficacy. reduces mRNA through methylation, thereby enhancing which contributes suppressing progression via PI3K/Akt signaling pathway.
Язык: Английский
Процитировано
10
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Янв. 18, 2025
The current study established the first in vitro Encorafenib resistance protocol BRAF-mutated malignant melanoma (MM) cells and investigated resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress iron colorimetric assay. most resistant group, called A375-R, was determined treated with a constant dose of 10 nM over 3 months. viability, apoptosis, G0/G1 arrest reflected acquired chemoresistance. Autophagic Beclin LC3 proteins, AKT signaling increased A375-R. RNA-Seq results also exhibited altered epigenetic regulation resistance; particularly ferritin family members, ion transport pathways. Then, NCOA4, FTH1, levels detected A375-R suggest that metabolism-related mechanism, such as ferritinophagy, might be triggered, which supported by TEM analysis. Iron storage, transport, ferritinophagy have promising potential to targeted for combining BRAF-targeted therapy reverse MM. Moreover, this is evaluating mechanisms, we our findings contribute improving new drug combinations targeting BRAF metabolism different MM cells.
Язык: Английский
Процитировано
1
Biomolecules, Год журнала: 2024, Номер 14(11), С. 1443 - 1443
Опубликована: Ноя. 13, 2024
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical pathway in cancer biology. This review delves into the epigenetic mechanisms that modulate ferroptosis cells, focusing on how DNA methylation, histone modifications, and non-coding RNAs influence expression function essential genes involved this process. By unraveling complex interplay between these ferroptosis, article sheds light novel gene targets functional insights could pave way for innovative treatments to enhance therapeutic efficacy overcome resistance therapy.
Язык: Английский
Процитировано
6
Cancer Letters, Год журнала: 2024, Номер unknown, С. 217350 - 217350
Опубликована: Ноя. 1, 2024
Pancreatic cancer remains one of the most challenging malignancies to treat due its late-stage diagnosis, aggressive progression, and high resistance existing therapies. This review examines latest advancements in early detection, therapeutic strategies, with a focus on emerging biomarkers, tumor microenvironment (TME) modulation, integration artificial intelligence (AI) data analysis. We highlight promising including microRNAs (miRNAs) circulating DNA (ctDNA), that offer enhanced sensitivity specificity for early-stage diagnosis when combined multi-omics panels. A detailed analysis TME reveals how components such as cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM) contribute therapy by creating immunosuppressive barriers. also discuss interventions target these components, aiming improve drug delivery overcome evasion. Furthermore, AI-driven analyses are explored their potential interpret complex data, enabling personalized treatment strategies real-time monitoring response. conclude identifying key areas future research, clinical validation regulatory frameworks AI applications, equitable access innovative comprehensive approach underscores need integrated, outcomes pancreatic cancer.
Язык: Английский
Процитировано
6
Biotechnology and Applied Biochemistry, Год журнала: 2025, Номер unknown
Опубликована: Янв. 7, 2025
ABSTRACT Dual inhibition of Akt and MEK1 pathways offers a promising strategy to enhance treatment efficacy in gastric cancer. In this study, we employed computational approaches followed by vitro validations. Our results demonstrate that SBL‐027 exhibits robust enduring interactions with kinases, as evidenced atomistic molecular dynamics simulations mechanics Poisson–Boltzmann surface area (MM‐PBSA) based binding free energy estimates. The predicted Gibbs energies indicate highly favorable between both kinases. vitro, displayed an IC 50 value 195.20 nM against 239.10 enzymes. compound exhibited potent cell proliferation KATOIII SNU‐5 cells, GI values 490.70 615.14 nM, respectively. Moreover, induced increase the sub G 0 /G 1 population during cycle while facilitating early late‐phase apoptosis these lines. Notably, significantly reduced percentage dual‐positive cells expressing cancer cells. strong affinity, stability, thermodynamics along established highlight its potential lead for further preclinical clinical development.
Язык: Английский
Процитировано
0
Biomolecules, Год журнала: 2025, Номер 15(2), С. 247 - 247
Опубликована: Фев. 8, 2025
N6-methyladenosine (m6A) is the most prevalent internal chemical modification in eukaryotic messenger RNA (mRNA), significantly impacting its lifecycle through dynamic and reversible processes involving methyltransferase, demethylase, binding proteins. These regulate mRNA stability, splicing, nuclear export, translation, degradation. Programmed cell death (PCD), a tightly controlled process encompassing apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, plays crucial role maintaining cellular homeostasis, tissue development, function. Recently, m6A has emerged as significant research area due to regulating PCD implications cardiovascular diseases (CVDs). In this review, we delve into intricate relationship between various types modification, emphasizing their pivotal roles initiation progression of CVDs such myocardial ischemia-reperfusion (I/R), atherosclerosis (AS), pulmonary hypertension (PH), cardiomyopathy, doxorubicin (Dox)-induced cardiotoxicity (DIC), heart failure (HF), infarction (MI). Our findings underscore potential elucidating CVD pave new pathways for prevention treatment strategies.
Язык: Английский
Процитировано
0
iScience, Год журнала: 2025, Номер 28(3), С. 112015 - 112015
Опубликована: Фев. 17, 2025
Pancreatic β cells exist in low and high insulin gene activity states that are dynamic on a scale of hours to days. Here, we used live 3D imaging, mass spectrometry proteomics, targeted perturbations cell signaling comprehensively investigate Ins2(GFP)HIGH Ins2(GFP)LOW states. We identified the two Ins2 intact isolated islets showed same state were more likely be nearer each other. report proteomes pure depth 5555 proteins show with had reduced immaturity factors, as well increased translation. activators cAMP (GLP1, IBMX) powerful drivers transitions. Okadaic acid cyclosporine A opposite effects. This study provides new insight into proteomic profiles regulation
Язык: Английский
Процитировано
0
The Journal of Gene Medicine, Год журнала: 2025, Номер 27(2)
Опубликована: Фев. 1, 2025
ABSTRACT Background Gliomas currently have a poor prognosis and limited therapy options. Betulinic acid (BA) has demonstrated antitumor activity in various cancers. This study is aimed at clarifying the underlying mechanisms by which BA inhibits gliomas. Methods We assessed how affected migration, apoptosis, invasion, proliferation, viability of U251 glioma cells. The genes that were differentially expressed after treatment identified via RNA sequencing. Utilizing Gene Ontology Kyoto Encyclopedia Genes Genomes, research was done to determine pathways. Molecular docking applied explore interaction with key pathway molecules. Experimental assays conducted confirm impact on these pathways targets. Results In cells, reduced viability; inhibited colony formation, invasion; triggered apoptosis. Through sequencing, 923 up‐ 1469 downregulated found, notable enrichment TNF, PI3K‐Akt, ferroptosis can stably bind TNF PI3K‐Akt molecules, especially AKT1 (binding energy = −10.2 kcal/mol). administration decreased levels phosphorylated PI3K AKT. Moreover, BA‐induced HO‐1 NRF2 increased. Ferrostatin‐1 zinc protoporphyrin pretreatment intracellular iron lipid peroxidation decrease cell caused BA. Conclusions controls PI3K/Akt NRF2/HO‐1 pathways, results ferroptosis. Understanding BA's multipathway mechanism may inform its therapeutic potential treatment.
Язык: Английский
Процитировано
0
Cancer Cell International, Год журнала: 2025, Номер 25(1)
Опубликована: Март 7, 2025
Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, playing critical role in various diseases, including cancer, neurodegeneration, and tissue damage. This study reviews the intricate relationship between ferroptosis Janus kinase/signal transducer activator transcription (JAK/STAT) signaling pathway, highlighting its regulatory functions across multiple biological processes. Dysregulation JAK/STAT pathway implicated promoting or inhibiting ferroptosis, depending on context. JAK2 promotes activating STAT proteins, modulating expression key regulators like SLC7A11 GPX4, influencing iron homeostasis through pathways such as ferritinophagy hepcidin regulation. STAT1 activation primarily enhances suppression cystine-glutamate antiporter (System Xc-), leading to glutathione depletion contributing conditions Sjogren's syndrome age-related macular degeneration. In contrast, STAT3 plays protective upregulating which inhibits survival, particularly cancers hepatocellular carcinoma, prostate renal carcinoma. also discusses STAT6's involvement diseases asthma lung injury regulating antioxidant defenses. Furthermore, review explores potential therapeutic strategies targeting manipulate for disease treatment. cancer therapy, this can enhance effectiveness inducers, offering promising avenues overcome drug resistance. Additionally, interplay immune responses, oxidative stress, metabolism underscores significance progression intervention. By exploring these mechanisms, provides insights into development novel treatments modulation, with implications inflammatory neurodegenerative conditions.
Язык: Английский
Процитировано
0
Biomolecules, Год журнала: 2025, Номер 15(3), С. 380 - 380
Опубликована: Март 5, 2025
Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only small fraction of identified medicinal plants has thoroughly investigated, particularly their effects on cellular pathways lung colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses the signaling modulated by bioactive compounds from eleven traditional plants: Curcuma longa, Astragalus membranaceus, Glycyrrhiza glabra, Althaea officinalis, Echinacea purpurea, Sanguinaria canadensis, Codonopsis pilosula, Hydrastis Lobelia inflata, Scutellaria baicalensis, Zingiber officinale. These were selected based documented use medicine clinical practice. Selection criteria involved cross-referencing herbs scoping treatments findings an international survey herbal currently management our research group availability existing literature properties. The identifies several isolated phytoconstituents these that exhibit properties modulating key such as PI3K/Akt/mTOR, RAS/RAF/MAPK, Wnt/β-catenin, TGF-β vitro. Notable constituents include sanguinarine, berberine, hydrastine, lobeline, curcumin, gingerol, shogaol, caffeic acid, echinacoside, cichoric glycyrrhizin, 18-β-glycyrrhetinic astragaloside IV, lobetyolin, licochalcone A, baicalein, baicalin, wogonin, glycyrol. Curcumin baicalin show preclinical effectiveness but face bioavailability challenges, which may be overcome combining them piperine or using oral extracts enhance gut microbiome conversion, integrating knowledge strategies improved outcomes. Furthermore, Echinacea, Glycyrrhiza, Codonopsis, knowledge, are trials. Notably, curcumin also modulate miRNA pathways, highlighting promising intersection science medicine. Thus, development therapeutics continues benefit synergy scientific innovation, technological advancements.
Язык: Английский
Процитировано
0