Nitric oxide initiates progression of human melanoma via a feedback loop mediated by apurinic/apyrimidinic endonuclease-1/redox factor-1, which is inhibited by resveratrol
Bibliographic record
Abstract
It is well recognized that nitric oxide (NO) is involved in tumor progression, including melanoma. Measurement of proliferative and metastatic capacity by MTS and Matrigel invasion assays, respectively, was done and showed that NO-treated melanoma cells exhibited a higher capacity compared with control, especially metastatic Lu1205 cells. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) is a multifunctional protein and its role in tumor biology has attracted considerable attention. To determine whether APE/Ref-1 plays a role in mediating NO stimulation of melanoma progression, we investigated the effect of DETA/NO on levels of APE/Ref-1 and related downstream targets [activator protein-1 (AP-1)/JunD, matrix metalloproteinase-1 (MMP-1), Bcl-2, and inducible nitric oxide synthase (iNOS)] by Western blot and reverse transcription-PCR analysis. Following DETA/NO treatment, APE/Ref-1 and other downstream molecules were induced. Knockdown of APE/Ref-1 or AP-1/JunD by specific small interfering RNA markedly reversed the induction by NO stress of target proteins. These results present evidence for the existence of a functional feedback loop contributing to progression and metastasis of melanoma cells. Resveratrol has been shown to be an APE/Ref-1 inhibitor and significant decreases in AP-1/JunD, MMP-1, Bcl-2, and iNOS protein levels occurred after exposure to resveratrol. This phenolic antioxidant may be an appropriate choice for combining with other compounds that develop resistance by up-regulation of these molecules.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".