Lavandula stoechas Ethanol Extracts Induce Apoptosis in Breast, Bladder, and Glioblastoma Cancer Cells

Background: Lavandula stoechas has attracted increasing attention for its potential anticancer properties; however, evidence regarding its effects on apoptotic signaling across different tumor types remains limited. Methods: In this study, the effects of dry and fresh ethanol extracts of Lavandula stoechas L. subsp. stoechas (LsDE and LsFE) were investigated in MDA-MB-231 triple-negative breast cancer, RT4 bladder carcinoma, and T98G glioblastoma cell lines, providing a comparative evaluation of their apoptotic effects. Long-term proliferative capacity was assessed using clonogenic survival assays, while apoptosis-related responses were evaluated by Annexin V–FITC/propidium iodide staining, quantitative RT-PCR of BAX and BCL2 and Western blot analysis of Bax, Bcl-2, and cleaved PARP1. Results: Both extracts significantly reduced clonogenic survival in all tested cancer cell lines, with LsDE showing stronger inhibitory effects in RT4 and T98G cells. Annexin V/PI analysis revealed cell type-dependent response patterns. In MDA-MB-231 cells, both extracts increased the proportion of PI-positive cells, suggesting a loss of membrane integrity, whereas RT4 cells exhibited increased early apoptotic and membrane-compromised populations. In contrast, T98G cells showed comparatively limited changes associated with apoptosis. Transcriptional analysis demonstrated extract- and cell line-specific modulation of the BAX/BCL2 ratio. Western blot analysis further demonstrated activation of mitochondrial apoptotic signaling through coordinated regulation of Bax and Bcl-2 and increased PARP1 cleavage. LsFE showed the strongest apoptosis-associated changes in MDA-MB-231 cells, whereas LsDE showed stronger effects in T98G cells, while both extracts were effective in modulating these proteins in RT4 cells. Conclusions: These findings indicate that ethanol extracts of L. stoechas impair long-term proliferative capacity and induce tumor type-dependent modulation of apoptosis-related markers. This study provides an integrated experimental framework that combines clonogenic survival assays, apoptosis analyses, gene expression, and protein-level measurements, supporting further investigation of L. stoechas extracts in cancer research.