Guru, S. K. | bioRxiv Science

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

Comparative Evaluation of Conventional Inorganic Fertilization and Sesbania rostrata Green Manuring on Soil Properties and the Growth and Development of Oryza sativa L. Pant Basmati 1

To assess the impacts of conventional and organic nutrient management techniques on growth, productivity, sustainability, and soil health in the Basmati rice (Oryza sativa L.) cultivar Pant Basmati 1, a two-year field experiment was carried out during the Kharif seasons of 2023 and 2024. Crop duration remained stable across management methods, as illustrated by phenological variables such as panicle initiation (58-62 days), blooming (84-88 days), and maturity (106-111 days) that were not significantly affected by fertilizer source. Conventional fertilizer supported superior growth at later stages, while organic management produced greater plant height at early growth phases. While the leaf area index and dry matter accumulation were consistently higher under conventional management because of the quick availability of nutrients, tiller density remained similar across treatments (363-411 m-{superscript 2}). Despite statistically significant variations, chlorophyll a and b quantities peaked under organic inputs at 60 DAT. Higher biological and grain yields were obtained with conventional fertilization; however, yield variations between systems were generally insignificant over time. As soil fertility stabilized, organic management notably increased the harvest index in the second year, indicating improved assimilate partitioning. The findings show that organic nutrient management can provide benefits in terms of resource efficiency and environmental sustainability while maintaining yield parity with conventional systems during the early conversion phase. Organic management techniques improve soil quality. Compared with to conventional methods, organic management practices were found to have higher soil macro and micronutrient status, water-holding capacity, aggregate stability, and soil enzyme activity (DHA and acid & alkaline phosphatase). These results show that organic Basmati rice cultivation is a feasible and sustainable alternative to traditional nutrient management, even though it may take longer to reach maximum yield.

plant biology↗