Breast cancer
Glucose-Dependent Cytotoxic Responses in Triple-Negative Breast Cancer: Experimental and Transcriptomic Evidence of Metabolic Context and p38 MAPK-Associated Modulation
By Rahman I, Henidi H, Alshibli A and 8 others.
Abstract
Background
Triple-negative breast cancer exhibits substantial metabolic heterogeneity, which may influence therapeutic response. This study investigated whether thymoquinone, glabridin, and glycyrrhizic acid exhibit context-dependent cytotoxicity under glucose deprivation and hypoxia, and whether pharmacological inhibition of p38 MAPK modifies these responses.
Methods
MDA-MB-231 and MCF-7 cells were treated in 2D monolayer culture with thymoquinone, glabridin, glycyrrhizic acid, or doxorubicin under normoxic, glucose-deprived, and hypoxic conditions. Cell viability was assessed by MTT assay, and p38 involvement was explored using SB203580 co-treatment. Selectivity was assessed in MCF-10A cells. Thymoquinone silver-nanoparticles were also evaluated. Bulk TCGA-BRCA basal-like and receptor-defined TNBC cohorts and GSE118389 single-cell TNBC RNA-seq data were analyzed for glycolysis, hypoxia, p38 MAPK, epithelial-mesenchymal transition, stemness, and oxidative-stress signatures.