Carpobrotus edulis Flower Extract Exerts Cytotoxic and Apoptotic Effects on A-549 Lung Cancer Cells: Phytochemical Profiling and In Silico EGFR Interaction Screening

Medicinal plants serve as critical reservoirs of bioactive scaffolds for targeted cancer therapeutics. This study evaluated the antiproliferative potential of Carpobrotus edulis methanolic flower extract across a panel of human cancer cell lines, including pancreatic (Panc-1), breast (MCF-7), liver (HepG-2), and lung (A-549) malignancies. Screening assays revealed potent, dose-dependent cytotoxicity in an MTT-based viability assay, with A-549 lung cancer cells being the most sensitive of the four tested cancer cell lines (IC50 = 3.62 ± 0.34 μg/mL). Selectivity over non-malignant cells was not assessed. Flow cytometry showed an increase in the S-phase fraction and in Annexin V-positive cells, and ELISA showed higher Bax and p53 and lower Bcl-2 in extract-treated A-549 cells, consistent with apoptosis through the intrinsic pathway. The measured caspase-3 concentration was lower after treatment, and the assay does not distinguish pro-caspase-3 from cleaved caspase-3. Phytochemical profiling via GC-MS identified a diverse array of bioactive metabolites, predominantly triterpenoids, phytosterols, fatty acid derivatives, and cyclitols. To explore EGFR as a putative target, an in vitro EGFR kinase assay was combined with molecular docking and molecular dynamics (MD) simulations. Among the profiled metabolites, the cyclitol derivative mome inositol displayed the most favorable docking score binding affinity toward the EGFR kinase domain (−7.35 kcal/mol), establishing robust hydrogen-bonding networks with key catalytic residues within the active site. Furthermore, a 100 ns MD simulation revealed the relative thermodynamic stability of the mome inositol–EGFR complex with more favorable RMSD, RMSF, hydrogen bond and radius of gyration profiles than the co-crystallized reference ligand. Collectively, these integrated in vitro, phytochemical, and in silico findings indicate that methanolic extract of C. edulis flowers exerts potent anticancer activity predominantly through mitochondrial-mediated apoptosis complemented by a computationally predicted interaction between its major cyclitol constituent and the EGFR kinase domain. These results establish the extract as a promising early-stage anticancer lead and provide a clear rationale for advancing to mechanistic studies, with in vivo validation reserved for subsequent investigations.