Frontiers in bioscience (Landmark edition) · 2025
Combined Schisandrin B and Temozolomide Treatment Induces Mitochondrial Apoptosis in Glioma Cells.
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Tang Zebo, Guo Chaoran, Wen Na, Jin Hong, Dong Yuan, Xu Bo, Ma Xiangyu, Han Liu, Liu Jianxin
Аннотация
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.
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.