Abstract B154: Thymoquinone causes mitochondrial membrane disruption and potentiates chemotherapeutic drug- and radiation-induced cytotoxicity in breast cancer cells
Bibliographic record
Abstract
Abstract Thymoquinone, which is the active constituent of the volatile oil extracted from black caraway seeds (Nigella sativa), has been reported to have antiinflammatory, antioxidant, and antineoplastic activities in vitro and in vivo. In this study we explored the mechanism by which thymoquinone inhibits breast cancer cell growth, as well as the potential of using thymoquinone in combination with conventional chemotherapeutic drugs or radiation therapy. Cytofluorimetric analysis of Oregon Green 488-stained MDA-MB-231 and MDA-MB-468 breast cancer cells following thymoquinone treatment demonstrated inhibition of cell proliferation. Colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays performed on MDA-MB-231, MDA-MB-468, and T-47D breast cancer cells after 24, 48, and 72 h treatment with thymoquinone (0.5–10 µM) showed a time- and dose-dependent cytotoxic effect, while untransformed human mammary epithelial cells were not adversely affected by thymoquinone. Longer exposure (144 h) to lower doses of thymoquinone (0.25–1 µM) was also cytotoxic for breast carcinoma cells. Importantly, staining of thymoquinone-treated breast cancer cells with annexin-V-FLUOS/propidium iodide indicated that cell death was by apoptosis. Western blot analysis of thymoquinone-treated breast cancer cells revealed increased cytosolic cytochrome c and PARP cleavage, which suggested induction of the mitochondrial pathway of apoptosis. However, broad spectrum caspase inhibitors (Bod-D and z-VAD-fmk) did not prevent thymoquinone-induced cytotoxicity, implying caspase-independent cell death. Thymoquinone treatment also sensitized breast cancer cells to γ-radiation and the conventional chemotherapeutic agents docetaxel and cisplatin. We conclude that thymoquinone caused caspase-independent apoptosis in breast cancer cells that involved the loss of mitochondrial membrane integrity. Furthermore, the ability of thymoquinone to potentiate the cytotoxic effects of chemotherapeutic drugs and -radiation may have application in a clinical setting. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B154.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".