Magnolol Traverses the Blood-brain Barrier and Enhances Temozolomide-induced Intrinsic Apoptosis of Glioblastoma Cells <i>via</i> a p53 Redox Signaling Mechanism
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND/AIM: , enhances TMZ-induced apoptosis in glioblastoma cells and explored the underlying mechanisms. MATERIALS AND METHODS: The safety of magnolol was evaluated in normal human astrocytes and mouse cerebral endothelial cells (CECs). Its ability to traverse the CEC tight junction barrier was examined, followed by assessments of its effects on TMZ-induced apoptosis in human and mouse glioblastoma cells. Mechanistic studies focused on p53 redox signaling. RESULTS: Magnolol at non-toxic concentrations crossed the CEC barrier and significantly potentiated TMZ-induced apoptosis in glioblastoma cells. Cotreatment decreased mitochondrial membrane potential, enhanced caspase-9 activity, and activated downstream caspases-3 and -6. Inhibition of caspase-9 or p53 phosphorylation attenuated magnolol's enhancement of TMZ-induced DNA fragmentation and apoptosis. Magnolol also elevated intracellular reactive oxygen species (ROS) levels, which further promoted p53 phosphorylation and apoptotic signaling. These synergistic effects were confirmed in both human U87MG and mouse GL261 glioblastoma cells. CONCLUSION: Magnolol traverses the CEC barrier and amplifies TMZ-induced apoptosis in glioblastoma cells through an intrinsic ROS-p53-caspase signaling cascade. Given its safety toward normal astrocytes and endothelial cells, magnolol represents a promising adjuvant strategy to improve TMZ-based therapy, potentially mitigating drug resistance and adverse effects in GBM treatment.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it