Combined Schisandrin B and Temozolomide Treatment Induces Mitochondrial Apoptosis in Glioma Cells.

BACKGROUND

Temozolomide (TMZ) is a standard chemotherapeutic agent for glioma, but prolonged use frequently leads to drug resistance, reducing its therapeutic efficacy. Schisandrin B (Sch B), a lignan isolated from Schisandra chinensis, demonstrates promising anti-neoplastic activity. This study investigated the synergistic effects of Sch B and TMZ on U87 glioma cells to explore their combined influence on cell viability, apoptosis, and mitochondrial function.

METHODS

U87 glioma cells were treated with Sch B, TMZ, or their combination. Cell viability was assessed using MTT assays. Apoptosis was evaluated by Hoechst staining and flow cytometry, while JC-1 staining and Western blotting were used to assess mitochondrial membrane potential, oxidative stress markers, and apoptosis-related proteins. Cell cycle analysis and pre-treatment with Z-VAD-FMK were performed to confirm pathway involvement.

RESULTS

Combination treatment significantly reduced cell viability (54.14%) compared to TMZ (72.47%) or Sch B (70.4%) alone. Flow cytometry indicated elevated apoptosis (22.3%) in the combination group. JC-1 staining and protein expression analyses revealed mitochondrial depolarization, cytochrome c release, activation of caspase-3 and -9, and a decreased Bcl-2/Bax ratio. The combined treatment induced G2/M cell cycle arrest via p53/p21 activation and increased oxidative stress. Pre-treatment with Z-VAD-FMK partially reversed these effects, confirming caspase-dependent mitochondrial apoptosis.

CONCLUSIONS

Sch B enhances TMZ-induced cytotoxicity in U87 glioma cells by promoting mitochondrial dysfunction, oxidative stress, and caspase-mediated apoptosis. These findings suggest that Sch B may serve as a promising adjuvant to improve the efficacy of TMZ-based glioma therapy, warranting further validation in resistant and in-vivo models.