Biology subjects

Chatterjee, E.

Publications and source records attributed to Chatterjee, E..

3 recordsLinked to original sources

bioRxiv2026

Unveiling Gloriosine as a Dual-Acting Regulator of Glutamine Metabolism and Ferroptosis in Triple-Negative Breast Cancer: Insights from Network Pharmacology and Experimental Validation

BackgroundTNBC lacks clearly defined molecular targets, so chemotherapy remains the standard approach despite resistance, toxicity, and high relapse rates. New, less toxic therapeutic options are urgently needed. This study evaluated the anticancer potential of gloriosine, a plant-derived alkaloid known to inhibit tumor cell growth with minimal effect on normal breast cells. MethodsPutative targets of gloriosine were predicted using SwissTargetPrediction, TargetNet, and PharmMapper, then intersected with gene sets linked to TNBC and glutamine metabolism. The resulting network was characterized through protein-protein interaction mapping and Gene Ontology/KEGG enrichment analysis. Molecular docking assessed binding affinity to top targets, and predictions were validated experimentally using cell viability, colony formation, and wound-healing assays. Oxidative stress and ferroptosis were assessed via ROS (DCFDA), glutathione, and lipid peroxidation (MDA) assays, along with Western blotting and FerroOrange staining. ResultsNetwork analysis identified 100 predicted targets, 60 overlapping with TNBC/glutamine-metabolism genes; SRC, EGFR, mTOR, and HSP90AA1 emerged as hub proteins. Enrichment analysis linked this network to cancer progression, metabolic reprogramming, and resistance pathways, including central carbon metabolism and ErbB/EGFR-inhibitor resistance signaling. Docking confirmed strong gloriosine-target binding. Experimentally, gloriosine reduced cell proliferation and migration in a dose-dependent manner. Mechanistically, it suppressed glutaminolysis and induced ferroptosis, marked by increased ROS, glutathione depletion, elevated lipid peroxidation, GPX4 suppression, and intracellular iron accumulation. ConclusionsGloriosine suppresses TNBC growth via multi-target modulation and ferroptosis induction, supporting its potential as a novel anticancer candidate. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/725321v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@aaebf6org.highwire.dtl.DTLVardef@16988bforg.highwire.dtl.DTLVardef@190db4dorg.highwire.dtl.DTLVardef@12dc2fd_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Flow chart of the network pharmacological and in vitro study of gloriosine C_FIG

cancer biology↗

bioRxiv2025

A role of extracellular vesicle-mediated inter-organ communication in obesity-related arrhythmia

Obesity contributes to the risk of cardiac arrhythmias, but the exact mechanism remains unclear. Here, we show visceral adipose tissue-derived extracellular vesicles (VAT EVs) from individuals with obesity prolong action potential duration (APD) and impair calcium handling in stem cell-derived cardiomyocytes, in addition to activating fibroblasts and macrophages towards a pro-fibrotic/inflammatory state, thereby creating pro-arrhythmic substrate. Adipose-derived EVs target the heart in obese mice, suggesting the potential for direct communication. Transcriptome-wide genetic association (TWAS) and epigenetic studies anchored on genes differentially expressed in cardiomyocytes, fibroblasts, and macrophages after VAT-EV exposure identified genes significantly associated with QT interval and atrial fibrillation. Finally, as a proof-of-principle, we pharmacologically blocked TRPC3 (a VAT-EV-induced ion channel) in cardiomyocytes, restoring the APD towards normality. This molecular genetic evidence supports an EV-mediated direct communication pathway between adipose tissue and the heart in arrhythmogenesis, offering a new paradigm to identify mediators of cardiovascular disease in obesity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/676027v1_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@114b230org.highwire.dtl.DTLVardef@1be7926org.highwire.dtl.DTLVardef@3d6b0org.highwire.dtl.DTLVardef@3ef15_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Exomap1 mouse: a transgenic model for in vivo studies of exosome biology

Exosomes are small extracellular vesicles (sEVs) of [~]30-150 nm in diameter that have the same topology as the cell, are enriched in selected exosome cargo proteins, and play important roles in health and disease. To address large unanswered questions regarding exosome biology in vivo, we created the exomap1 transgenic mouse model. In response to Cre recombinase, exomap1 mice express HsCD81mNG, a fusion protein between human CD81, the most highly enriched exosome protein yet described, and the bright green fluorescent protein mNeonGreen. As expected, cell type-specific expression of Cre induced the cell type-specific expression of HsCD81mNG in diverse cell types, correctly localized HsCD81mNG to the plasma membrane, and selectively loaded HsCD81mNG into secreted vesicles that have the size ([~]80 nm), topology (outside out), and content (presence of mouse exosome markers) of exosomes. Furthermore, mouse cells expressing HsCD81mNG released HsCD81mNG-marked exosomes into blood and other biofluids. Using high-resolution, single-exosome analysis by quantitative single molecule localization microscopy, we show here that that hepatocytes contribute [~]15% of the blood exosome population whereas neurons contribute <1% of blood exosomes. These estimates of cell type-specific contributions to blood EV population are consistent with the porosity of liver sinusoidal endothelial cells to particles of [~]50-300 nm in diameter, as well as with the impermeability of blood-brain and blood-neuron barriers to particles >5 nm in size. Taken together, these results establish the exomap1 mouse as a useful tool for in vivo studies of exosome biology, and for mapping cell type-specific contributions to biofluid exosome populations. In addition, our data confirm that CD81 is a highly-specific marker for exosomes and is not enriched in the larger microvesicle class of EVs.

cell biology↗