Doxorubicin (DOX) and lapatinib (LAP) have been reported to cause liver toxicity. The roles of mitochondrial and cellular responses in DOX and LAP mediated-hepatotoxicity have not been investigated with or without quercetin (QUE) in HepG2 cells sensitive to mitochondrial damage (high-glucose or galactose media) in addition to studies. Our results revealed that cytosolic pathways might play role a in DOX-induced cytotoxicity rather than mitochondria. QUE exacerbated DOX-induced ATP depletion in both environments. Our data also indicated that cytosolic and mitochondrial pathways might play a role in LAP-induced cytotoxicity. Incubating QUE with LAP increased ATP levels in high-glucose media. Therefore, QUE might have protective effect against LAP-induced cytotoxicity resulting from cytosolic pathways. The findings from experiments that QUE increased DOX or LAP-induced mitochondrial dysfunction were confirmed by the results from studies indicating that QUE incubated with LAP or DOX might increase mitochondrial dysfunction.

Download full-text PDF

Source
http://dx.doi.org/10.1080/1120009X.2025.2471154DOI Listing

Publication Analysis

Top Keywords

cytosolic pathways
8
pathways play
8
play role
8
lap-induced cytotoxicity
8
mitochondrial dysfunction
8
mitochondrial
6
exploring role
4
role quercetin
4
quercetin doxorubicin
4
doxorubicin lapatinib-mediated
4

Similar Publications

Small interfering RNA (siRNA) has garnered tremendous interest as a potential therapeutic tool because of its intriguing gene-silencing ability. Toward the success in the manufacture of siRNA therapeutics for the potential treatment of choroidal neovascularization (CNV), siRNA conjugated with dual functional units of membrane-penetrating heptafluoropropyl and age-related macular degeneration-targeting cyclic Arg-Gly-Asp (RGD) peptide was attempted for transcellular transportation into the cell interiors. Of note, cyclic RGD allowed selective affinities toward the angiogenic endothelial cells in the pathological CNV.

View Article and Find Full Text PDF

The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.

Cell Mol Life Sci

March 2025

Institute for Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Medizinisch-Theoretisches Zentrum MTZ, Technische Universität Dresden, Fiedlerstraße 42, 01307, Dresden, Germany.

Signal peptide peptidase (SPP) is an ER-resident aspartyl intramembrane protease cleaving proteins within type II-oriented transmembrane segments. Here, we identified the tail-anchored protein Three prime repair exonuclease 1 (TREX1) as a novel substrate of SPP. Based on its DNase activity, TREX1 removes cytosolic DNA acting as a negative regulator of the DNA-sensing cGAS/STING pathway.

View Article and Find Full Text PDF

P-bodies (PBs) and stress granules (SGs) are conserved, non-membranous cytoplasmic condensates of RNA-protein complexes. PBs are implicated in post-transcriptional regulation of gene expression through mRNA decay, translational repression and/or storage. Although much is known about the de novo formation of PBs and SGs involving liquid-liquid phase separation through multiple protein-protein and protein-RNA interactions, their subcellular localization and turnover mechanisms are less understood.

View Article and Find Full Text PDF

Cellular calcium homeostasis and regulation of its dynamic perturbation.

Quant Plant Biol

February 2025

Marine Biological Association, The Laboratory, Citadel Hill, Plymouth, UK.

Calcium ions (Ca) play pivotal roles in a host of cellular signalling processes. The requirement to maintain resting cytosolic Ca levels in the 100-200 nM range provides a baseline for dynamic excursions from resting levels that determine the nature of many physiological responses to external stimuli and developmental processes. This review provides an overview of the key components of the Ca homeostatic machinery, including known channel-mediated Ca entry pathways along with transporters that act to shape the cytosolic Ca signature.

View Article and Find Full Text PDF

Background: Limited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors.

Methods: 50 HPV+ OPSCCs that later recurred (cases) and 50 non-recurrent controls matched for stage, therapy, and smoking history were RNA-sequenced.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!