Melatonin increases 5-flurouracil-mediated apoptosis of colorectal cancer cells through enhancing oxidative stress and downregulating survivin and XIAP
Bibliographic record
Abstract
Introduction: Colorectal cancer (CRC) is one of the most lethal human malignancies with a global alarming rate of incidence. The development of resistance against common chemotherapeutics such as 5-fluorouracil (5-FU) remains a big burden for CRC therapy. Therefore, we investigated the effects of melatonin on the increasing 5-FU- mediated apoptosis and its underlying mechanism in SW-480 CRC cell line. Methods: The effects of melatonin and 5- FU, alone or in combination, on cell proliferation were evaluated using an MTT assay. Further, Annexin-V Flow cytometry was used for determining the effects of melatonin and 5-FU on the apoptosis of SW-480 cell lines. The expression levels of Bax, Bcl-2, pro-caspase-3/activated caspase 3, X-linked inhibitor of apoptosis proteins (XIAP), and survivin were measured after 48 hours incubation with drugs. Cellular levels of reactive oxygen species (ROS), catalase, superoxide dismutase and glutathione peroxidase were also evaluated. Results: Melatonin and 5-FU significantly decreased the cell proliferation of SW-480 cells. Combination of 5-FU with melatonin significantly decreased the IC50 value of 5-FU from 100 μM to 50 μM. Moreover, combination therapy increased intracellular levels of ROS and suppressed antioxidant enzymatic activities (P < 0.05). Treatment with either melatonin or 5-FU resulted in the induction of apoptosis in comparison to control (P > 0.05). XIAP and survivin expression levels potently decreased after combination treatment with melatonin and 5-FU (P < 0.05). Conclusion: We demonstrated that melatonin exerts a reversing effect on the resistance to apoptosis by targeting oxidative stress, XIAP and survivin in CRC cells. Therefore, more studies need for better understanding of underlying mechanisms for beneficial effects of combination of melatonin and 5-FU.
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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 | 0.001 |
| 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".