Oncogenic signaling in the Drosophila prostate-like accessory gland activates a pro-tumorigenic program in the absence of proliferation

Disease Models & Mechanisms, Journal Year: 2025, Volume and Issue: 18(4)

Published: April 1, 2025

ABSTRACT Drosophila models for tumorigenesis have revealed conserved mechanisms of signaling involved in mammalian cancer. Many these use highly mitotically active tissues. Few adult tissues, when most cells are terminally differentiated and postmitotic. The accessory glands prostate-like a model prostate using this tissue has been explored. In prior model, oncogenic was induced during the proliferative stages gland development, raising question how activity impacts differentiated, postmitotic tissue. Here, we show that leads to activation pro-tumorigenic program, similar mitotic but absence proliferation. our experiments, led hypertrophy with nuclear anaplasia, part through endoreduplication. Oncogene-induced gene expression changes overlapped those polyploid cancer after chemotherapy, which potentially mediate tumor recurrence. Thus, provide useful aspects progression lack cellular

Language: Английский

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Silibinin alleviates intestinal inflammation via inhibiting JNK signaling in Drosophila

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 14, 2023

Inflammatory bowel diseases (IBDs) are characterized by chronic relapsing intestinal inflammation that causes digestive system dysfunction. For years, researchers have been working to find more effective and safer therapeutic strategies treat these diseases. Silibinin (SIL), a flavonoid compound extracted from the seeds of milk thistle plants, possesses multiple biological activities is traditionally applied liver SIL also widely used in treatment variety inflammatory attributed its excellent antioxidant anti-inflammatory effects. However, efficacy against IBDs mechanisms remain unclear. In this study, using Drosophila melanogaster as model organism, we found can effectively relieve caused dextran sulfate sodium (DSS). Our results suggested supplementation inhibit overproliferation stem cells (ISCs) induced DSS, protect barrier function, acid-base balance, excretion reduce reactive oxygen species (ROS) levels stress, extend lifespan Drosophila. Furthermore, our study demonstrated ameliorates via modulating c-Jun N-terminal kinase (JNK) signaling pathway research aims provide new insight into IBDs.

Language: Английский

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Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(7), P. 714 - 727

Published: Feb. 21, 2024

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths. Increased activity the epidermal growth factor receptor (EGFR) often observed in pancreatic cancer, and small molecule EGFR inhibitor erlotinib has been approved for therapy by food drug administration. Nevertheless, alone ineffective should be combined with other drugs to improve therapeutic outcomes. We previously showed that certain tyrosine kinase inhibitors can increase mitochondrial membrane potential (Δψm), facilitate tumor cell uptake Δψm-sensitive agents, disrupt homeostasis, subsequently trigger death. Erlotinib not tested this effect. AIM To determine whether elevate Δψm triggering METHODS fluorescent dye was used how affects adenocarcinoma (PDAC) lines. The viability conventional patient-derived primary PDAC lines 2D- 3D cultures measured after treating cells sequentially mitochondria-targeted ubiquinone (MitoQ), MitoQ. synergy between MitoQ then analyzed using SynergyFinder 2.0. preclinical efficacy two-drug combination determined immune-compromised nude mice bearing line xenografts. RESULTS elevated cells, facilitating enrichment agents. triggered caspase-dependent apoptosis culture if at high doses, while pretreatment potentiated low doses suggested these synergistically induced lethality. Consistent vitro data, suppressed human xenografts more effectively than single treatments each agent. CONCLUSION Our findings suggest suppress effectively.

Language: Английский

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Intestinal stem cells and their niches in homeostasis and disease

Cells and Development, Journal Year: 2023, Volume and Issue: 175, P. 203862 - 203862

Published: June 2, 2023

Language: Английский

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Hydrogen peroxide-induced oxidative damage and protective role of peroxiredoxin 6 protein via EGFR/ERK signaling pathway in RPE cells

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: July 17, 2023

Introduction Damage to retinal pigment epithelium (RPE) cells caused by oxidative stress is closely related the pathogenesis of several blinding diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, and other inherited degenerative conditions. However, mechanisms this process are poorly understood. Hence, goal study was investigate hydrogen peroxide (H 2 O )-induced damage protective role peroxiredoxin 6 (PRDX6) protein via EGFR/ERK signaling pathway in RPE cells. Methods Cells from a human cell line (ARPE-19 cells) were treated with H , then viability assessed using methyl thiazolyl tetrazolium assay. Cell death reactive oxygen species (ROS) detected flow cytometry. The levels PRDX6, epidermal growth factor receptor (EGFR), P38 mitogen-activated kinase (P38MAPK), c-Jun N-terminal (JNK), extracellular signal-regulated (ERK) Western blot PRDX6 EGFR also immunofluorescence staining. Results Our results show that inhibited viability, induced death, increased ROS ARPE-19 It found decreased EGFR, phosphorylated ERK but P38MAPK JNK. overexpression attenuate -induced inhibition production expression alleviated decrease ERK. Moreover, factor-induced partially blocked overexpression. Discussion findings indicate protects decreasing blocking stress. Therefore, shows promise therapeutic target for prevention associated diseases.

Language: Английский

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A Novel Synthesized Cyclohexane-Hydroxytyrosol Derivative Suppresses Ovarian Cancer Cell Growth Through Inducing Reactive Oxidative Species and Blocking Autophagic Flux

Antioxidants and Redox Signaling, Journal Year: 2024, Volume and Issue: 41(7-9), P. 430 - 461

Published: Feb. 26, 2024

Aims: Drug resistance in ovarian cancer (OC) cells often leads to recurrence, metastasis, and high mortality rates among OC patients. Hydroxytyrosol (HT) has been reported inhibit the proliferation of other types cells. Here we synthesized a novel cyclohexane-hydroxytyrosol derivative (Chx-HT) for enhanced anticaner efficacy. We examined growth-suppressing effect Chx-HT on vitro xenograft mouse model investigated underlying mechanism.

Language: Английский

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Theophylline derivatives promote primordial follicle activation via cAMP-PI3K/Akt pathway and ameliorate fertility deficits in naturally aged mice

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(13), P. 5312 - 5329

Published: Jan. 1, 2024

In elderly women and patients with premature ovarian insufficiency (POI), activating their remaining dormant primordial follicles

Language: Английский

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The MicroRNA miR-277 Controls Physiology and Pathology of the Adult Drosophila Midgut by Regulating the Expression of Fatty Acid β-Oxidation-Related Genes in Intestinal Stem Cells

Metabolites, Journal Year: 2022, Volume and Issue: 12(4), P. 315 - 315

Published: March 31, 2022

Cell division, growth, and differentiation are energetically costly dependent processes. In adult stem cell-based epithelia, cellular identity seems to be coupled with a cell's metabolic profile vice versa. It is thus tempting speculate that resident cells have distinct metabolism, different from more committed progenitors differentiated cells. Although investigated for many cell types in vitro, vivo data of niche-residing metabolism scarce. epithelial tissues, cells, progenitor their progeny very functions characteristics. our study, we hypothesized tested whether might distinctive the intestinal lineage. Here, taking advantage genetically accessible

Language: Английский

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Analysis of cell-specific transcriptional responses in human colon tissue using CIBERSORTx

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 25, 2023

Abstract Diet is an important determinant of overall health, and has been linked to the risk various cancers. To understand mechanisms involved, transcriptomic responses from human intervention studies are very informative. However, gene expression analysis biopsy material only represents average profile a mixture cell types that can mask more subtle, but relevant cell-specific changes. Here, we use CIBERSORTx algorithm generate single-cell multicellular colon tissue. We applied microarray data PHYTOME study, which investigated effects different meat on transcriptional biomarker changes colorectal cancer (CRC) risk. First, used mRNA sequencing healthy tissue novel signature matrix in CIBERSORTx, then determined proportions each separate type. After comparison, proportion showed continuous upward trend abundance goblet cells stem cells, downward transit amplifying after addition phytochemicals red products. The dietary influenced genes involved growth division metabolism detoxification enterocytes, translation glycosylation inflammatory response innate lymphoid cells. These results show our approach offers insights into heterogeneous during intervention.

Language: Английский

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Hyperdiploid acute lymphoblastic leukemia in children with LZTR1 germline variants

HemaSphere, Journal Year: 2024, Volume and Issue: 8(1)

Published: Jan. 1, 2024

Language: Английский

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