Abstract 1427: Sensitizing HL60 acute myeloid leukemia cells to decitabine with pterostilbene
Notice bibliographique
Résumé
Abstract Introduction. Decitabine (DAC), is a DNA hypomethylating agent that has been shown to be potent towards leukemia cells at low doses. However, many patients develop resistance to the drug due to dysregulation of genes associated with responsiveness to DAC-induced DNA demethylation. To this regard, it has been reported that downregulation of TET2, one of the demethylating enzymes, increases sensitivity to DAC in acute myeloid leukemia (AML) cells. Remarkably, dietary bioactive compounds such as pterostilbene (PTS), with a stilbenoid ring structure, have previously been shown to mediate changes in gene expression through regulation of the epigenetic machinery in cancer models. Thus, we sought to test the impact of treatment of leukemia cells with PTS to augment expression of genes involved in the responsiveness of low-dose DAC in AML cells. Methods. HL60, an AML cell line, was either treated in combination with PTS (1.0 µM) and DAC (200 nM) or pre-treated with different concentrations of PTS (0 µM, 0.5 µM, 1.0 µM, 2 µM) for four days followed by DAC treatment (100 nM) for three days. Cell growth was assessed via trypan blue dye exclusion test and comparisons were made between combination treatment and pre-treatment with PTS. qPCR was performed in triplicates for each assay to assess expression of selected genes. Results. Treatment of HL60 cells with 200 nM DAC alone led to a 60% decrease in cell growth compared to control (treated with ethanol as a vehicle). After the combined treatment with PTS, cell growth decreased by further 27% compared to DAC alone. In order to decipher if this decrease in cell growth was due to the effect of PTS sensitizing cells to DAC, the cells were first pre-treated with PTS for four days and subsequently treated with DAC for three days. Compared to control (ethanol pre-treated cells), growth of cells treated with 100 nM DAC alone was decreased by about 37%, while growth of cells pre-treated with 0.5 µM, 1.0 µM, and 2.0 µM PTS followed by 100 nM DAC exposure was further reduced by 13%, 14.5%, and 30%, respectively. This suggests that PTS-pre-treated cells are more sensitive to DAC. Interestingly, DAC alone at 200 nM led to an increase in expression of TET2 (p<0.01) while PTS at 1.0 µM alone led a decrease (p<0.01) compared to control. However, when PTS and DAC were combined, TET2 levels increased significantly (p<0.01) compared to both control and DAC alone, despite its better ability to inhibit growth. In order to explore this further, we will proceed with investigating the effects of pre-treatment with PTS on TET2 expression in HL60 cells. Conclusion. Treatment of HL60 cells with PTS results in improved sensitivity of cells to low doses of DAC, possibly due to modulating TET2 expression. Citation Format: Cayla Boycott, Barbara Stefanska. Sensitizing HL60 acute myeloid leukemia cells to decitabine with pterostilbene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1427.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».