Resveratrol mediates cell fate in human uterine cancer cells through prostaglandin inhibition
Bibliographic record
Abstract
751 In the Western world, endometrial cancer is the most common gynecologic cancer and is the fourth importance among all feminine cancers. Cyclooxygenase-1 and -2 (COX-1 and -2) are the limiting enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. The PGs have been shown to be implicated in evolution and tumor transformation, particularly, PGE2. Four prostaglandin E2 receptors have been found: EP1, EP2, EP3 and EP4. The aim of this study was to determine if resveratrol, a natural anti-oxidant found in red wine, could influence the production of PGs and apoptotic cell death or cellular proliferation. Six different human uterine cancer cell lines were used for this study. Real-time RT-PCR and Western analyses were carried out to measure COX-1, COX-2, EP1, EP2, EP3 and EP4 expression. The results indicated that all cell lines expressed both COX isoforms and the four EP receptors at different levels. In experiment two, cells were treated with various concentrations of resveratrol for different length of time. MTT proliferation assay revealed that resveratrol induced maximal cell proliferation of RL-95-2 cells in a dose dependent manner after 24 hours, which was reduced after 48 and 72 hours. Resveratrol had no effect on KLE cells in term of proliferation but inhibited cell proliferation in HeLa and HEC-1-A in a dose and time dependant manner. In Ishikawa and TOV-1078D cells, a novel human endometrial cancer cell line, the effect of resveratrol was biphasic: cell proliferation was increased at low concentration whereas higher concentrations resulted in a decreased of cell proliferation in a time dependent manner. Hoechst nuclear staining indicated that resveratrol induced apoptosis in HeLa, HEC-1-A, Ishikawa and TOV-1078D but not in KLE and RL-95-2 cells. Since we have showed that Akt activity can directly up-regulate COX-2 gene expression and PGE2 secretion, in experiment two Western blot analyses were carried out to determine the possible involvement of the PI3-K/PTEN/Akt pathway in this process. Results indicate that, depending on the cell line, resveratrol can act positively and negatively on Akt phosphorylation in those wild types (HeLa, HEC-1-A and KLE) and mutated PTEN (RL-95-2, Ishikawa and TOV-1078D) human uterine cancer cells and that COX-1 and COX-2 expressions are influenced by resveratrol. In response to resveratrol PGE2 secretion was decreased in HeLa, HEC-1-A and Ishikawa cells. The results suggest that resveratrol, through its action on prostaglandin biosynthesis, could be an important regulator of cell survival in uterine cancer. Supported by CIHR (MOP-66987).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".