In Vivo Molecular Modulation of P-AKT, XIAP, and COX-2 Pathways, and Cellular Proliferation by Resveratrol in Uteri of Immature Rats.
Bibliographic record
Abstract
Resveratrol (trans-3,4N-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with anticancer properties. Anticancerous properties of this antioxidant are exerted by antiproliferative and pro-apoptotic activities in various cancer cell types, but its molecular effect on uterine cells, both in normal and cancerous cells, is poorly understood. We have reported previously, that resveratrol can modulate COX-2 and AKT expressions/activities in endometrial cancer cells, and thus reverse cellular resistance associated with overexpression of these proteins. It has been reported that postnatal exposure to resveratrol may affect estrogenic activity in specific peripheral tissues (e.g. gonads), and differ from most other phytoestrogens by acting as a possible mixed ER agonist/antogonist, depending on the tissu-specific availability of ER subtypes. The aim of the present study was to investigate in vivo, in normal endometrial cells, if resveratrols protective effect would also involve COX-2 and AKT pathways, and/or ER. Healthy immature Sprague-Dowley rats were treated s.c. with resveratrol (0, 0.5, 5, 50 mg/kg/day) for 7 consecutive days, and sacrificed on the 8th day. Uteri were collected, weighted and endometrium was recovered for total protein extraction. Western blot analysis of protein expression were conducted and quantified. ER-alpha and beta affinity and activation by resveratrol were also determined by in vitro ER-binding and ERE-Luciferase activation assays. The results showed that 5.0 mg/kg body weight of resveratrol s.c. could increase uterine wet weight and uterine-body weight ratios significantly (P<0.05). This local cellular proliferation was accompanied by an increase of AKT phosphorylation and an increase of COX-2 and XIAP protein expression. AKT and ERs protein expression were not modulated by the treatment. Resveratrol showed moderate estrogenicity for both ER isoforms, low binding-affinity/activation, favouring ER-beta. In normal rats in vivo, resveratrol triggers phosphorylation of AKT and the downstream cascade involving XIAP and COX-2, stimulating proliferation of the epithelium and the glandular environment. Thus, thickening the columnar epithelial cells or an increase in the number of glands in endometrium of mature females could positively affect the outcome of pregnancy and favour fertility. These data support the hypothesis that resveratrol can act in a pro-survival or pro-apototic way, through AKT/p-AKT, XIAP and COX-2 regulation, depending on the localisation and the nature of the cells involved. Supported by NSERC (238501-06).
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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".