Selective Cytotoxicity of Ozone in Burkitt and Mantle Cell Lymphomas: Disruption of AURKA/B Pathways and Induction of Apoptosis

ABSTRACT Ozone (O3) therapy exerts selective cytotoxic effects on solid tumors via oxidative stress, yet its molecular impact on hematologic malignancies is not well defined. This study evaluated the effects of ozone on cell viability, apoptosis, oxidative stress, and the expression of mitotic and apoptotic regulators in Burkitt lymphoma (BL) and mantle cell lymphoma (MCL) compared to normal B lymphocytes. BL (CA46, RAJI) and MCL (MAVER-1, JVM-2) cell lines, along with primary CD19+ B cells, were exposed to ozonated RPMI-1640 medium (5–40 ng/mL) for 30 min. Ozone concentration was determined using the indigo colorimetric method. Viability (CCK-8), apoptosis (ELISA), ROS (fluorometric assay), and gene expression (RT-qPCR for TP53, CASP9, CASP3, BCL-2, AURKA, AURKB) were assessed at 24–72 h (p < 0.05). Ozone exposure reduced viability and increased apoptosis in a dose- and time-dependent manner, with BL lines being more sensitive. CASP9 and CASP3 were upregulated, while BCL-2, AURKA, and AURKB were downregulated, indicating intrinsic apoptotic and mitotic-disruption activation. ROS accumulation was higher in malignant than in normal cells, which remained largely unaffected. These findings suggest that ozone selectively targets B-cell lymphomas through oxidative and mitotic stress, supporting its potential as a low-cost adjunctive.