Exploring the Phytochemical Composition of Bitter Melon Fruit and Molecular Responses to Its Extract in U87 MG Glioblastoma Cells

Glioblastoma (GBM) is a highly aggressive type of brain cancer for which only a limited number of therapeutic options are available, highlighting the need to use multi-target strategies that interfere with the mechanisms by which the tumor survives and adapts to stress. In the present study, we investigated the antiproliferative and transcriptomic effects of bitter melon (Momordica charantia) extract (BME) in U87 MG glioblastoma cells. GC-MS analysis of bitter melon fruit revealed several bioactive metabolites known to have anticancer properties, including stigmasterol, β-sitosterol, caffeic acid, ferulic acid, and other fatty and organic acids, indicating that the extract has a chemically diverse composition that may explain its biological effects. BME markedly inhibited U87 MG cell proliferation in a dose- and time-dependent manner, with an IC50 of 659 µg/mL. Transcriptome analysis identified 908 differentially expressed genes, 380 upregulated and 528 downregulated. Functional and pathway analyses demonstrated enrichment in apoptosis, cellular senescence, ferroptosis, p53 signaling, and cellular stress responses, together with the suppression of PI3K–AKT, TNF, TGF-β, and cytokine–cytokine receptor signaling. The findings show that BME’s growth-inhibiting effect results from coordinated activation of cell-death and stress-response pathways along with reduced pro-tumor survival signaling. Combining metabolite profiling with transcriptomic analysis provides a molecular basis for identifying additional compounds in BME that are responsible for its antiproliferative action in glioblastoma and for verifying their effects.