Sholeh Javadi; Somayeh Farahmand; Helia Bayat; Reza HajiHosseini; Sima Nasri
Abstract
Triple-negative breast cancer (TNBC) lacks targetable receptors, rendering conventional chemotherapy the sole standard of care despite its associated toxicity and acquired resistance. The constitutively activated NF-κB and STAT3 signaling axes represent mechanistically interdependent oncogenic ...
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Triple-negative breast cancer (TNBC) lacks targetable receptors, rendering conventional chemotherapy the sole standard of care despite its associated toxicity and acquired resistance. The constitutively activated NF-κB and STAT3 signaling axes represent mechanistically interdependent oncogenic drivers in TNBC, making their simultaneous inhibition a compelling therapeutic strategy. β-Sitosterol, the predominant phytosterol of Allium cepa seeds, has demonstrated broad antiproliferative properties; however, its capacity for dual-target engagement against NFKB1 and STAT3 has not been systematically characterized. GC–MS profiling of A. cepa seed oil identified β-sitosterol as the principal constituent (80.45%). Computational ADMET analysis, Human Protein Atlas-based immunocytochemical target validation, and Auto Dock Vina molecular docking against NFKB1 (PDB: 5AX3) and STAT3 (PDB: 7LET) were performed. Anticancer activity was evaluated in MDA-MB-231 cells via MTT assay, with apoptotic mechanism characterized by Annexin V-FITC/PI flow cytometry. β-Sitosterol demonstrated favorable drug-likeness with predicted mitochondrial localization and absence of mutagenicity. Docking yielded binding energies of −7.0 and −6.7 kcal/mol for STAT3 and NFKB1, respectively, driven by hydrophobic interactions. MTT assay revealed concentration-dependent cytotoxicity (IC₅₀ = 39.56 µM; 72 h; F = 113.8, p < 0.0001). Flow cytometry confirmed significant induction of early (30.7 ± 2.5%) and late apoptosis (20.3 ± 4.4%) versus negligible baseline levels in controls. β-Sitosterol exhibits dual computational binding affinity for NFKB1 and STAT3 alongside potent pro-apoptotic activity in TNBC cells, establishing a mechanistic foundation for its further translational development.
Saber Samadiafshar; Somayeh Farahmand; Ali Nikakhtar; nadia Garmsiri; Farnia Garmsiri; Sahel Samadiafshar; Roghayeh Azizi
Abstract
Urinary tract infections represent a global health challenge increasingly complicated by antimicrobial resistance. This study explores the therapeutic potential of Stachys schtschegleevii essential oil against common uropathogens. Gas chromatographic-Mass Spectrometry analysis revealed four principal ...
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Urinary tract infections represent a global health challenge increasingly complicated by antimicrobial resistance. This study explores the therapeutic potential of Stachys schtschegleevii essential oil against common uropathogens. Gas chromatographic-Mass Spectrometry analysis revealed four principal bioactive compounds (α-Pinene, β-Pinene, Linalool, and Hexadecanoic Acid) exhibiting remarkable synergistic antimicrobial activity. Molecular docking simulations demonstrated exceptional binding affinities between these phytocompounds and bacterial dihydrofolate reductase enzymes, with α-Pinene and β-Pinene forming strongest complexes with Enterococcus faecalis DHFR (-6.1 kcal/mol) and Hexadecanoic Acid with Staphylococcus aureus DHFR (-6.1 kcal/mol). In vitro evaluation confirmed significant antimicrobial efficacy, with substantial inhibition zones (E. faecalis 20.16±0.2mm, E. coli 17.7±0.45mm, S. aureus 20.53±1.47mm) and impressive minimum inhibitory concentrations (E. faecalis 6.25mg/ml, E. coli 1.56mg/ml, S. aureus 3.12mg/ml). The multi-component nature of these extracts creates a complementary mechanism of action whereby multiple compounds simultaneously target different bacterial pathways, significantly reducing resistance development probability compared to single-compound therapeutics. This synergistic interaction, coupled with the plant's documented anti-inflammatory properties, presents schtschegleevii as an exceptional candidate for developing novel phytotherapeutic approaches against increasingly resistant uropathogens, offering an optimal balance of therapeutic efficacy, economic viability, and patient safety in urinary tract infection management.
