Abstract 3206: A novel prodrug of the green tea polyphenol (−)-epigallocatechin-3-gallate inhibits the telomerase gene by modifying DNA methylation and histone acetylation in breast cancer cells
Notice bibliographique
Résumé
Abstract Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols (GTPs), has been reported to down-regulate telomerase activity in breast cancer cells thereby increasing cellular apoptosis and inhibiting cellular proliferation. However, the major concerns with GTPs and EGCG are the bioavailability and poor stability under physiological conditions. In the present study, we have observed that treatments with EGCG and a novel pro-drug of EGCG (Pro-EGCG) dose-dependently inhibit the cellular proliferation of human breast carcinoma MCF-7 and MDA-MB-231 cells. Inhibition of telomerase has received wide attention in breast cancer prevention because of its unique expression in cancer cells and low level of expression in normal mammary epithelial cells. Both EGCG and Pro-EGCG inhibited the transcription of hTERT (human telomerase reverse transcriptase) by epigenetic modification in MCF-7 and MDA-MB-231 cells. The inhibition of hTERT expression was consistently correlated with hTERT promoter hypomethylation and deacetylation. Chromatin immunoprecipitation (ChIP) analysis of the hTERT promoter revealed that EGCG and Pro-EGCG increased the level of inactive trimethyl H3K9, but decreased active dimethyl H3K4 and acetyl H3K9. In addition, EGCG and Pro-EGCG significantly inhibited DNA methyltransferase (DNMT) activity, which might have an important role in the down-regulation of hTERT by demethylation of the CpG sites in the hTERT promoter in breast cancer cells. Bisulfite sequencing of the hTERT promoter confirmed the induced hypomethylation of the hTERT promoter by EGCG and Pro-EGCG. Down-regulation of hTERT was also mediated through significant inhibition of histone acetyltransferase (HAT), an enzyme responsible for histone acetylation, by EGCG and Pro-EGCG. Histone deacetylase (HDAC) activity was not altered by EGCG and Pro-EGCG, which reveals that EGCG- and Pro-EGCG-induced histone deacetylation was mediated through inhibition of HAT, but not by effects on HDACs in these breast cancer cells. These results show that EGCG and Pro-EGCG are inhibiting the cellular proliferation and inducing apoptosis in these breast carcinoma cells but not in normal control mammary epithelial MCF10A cells, at least in part, through epigenetic modification of telomerase expression. Further, our results also show that Pro-EGCG is more stable than EGCG and required a lesser dose than EGCG to facilitate the same cellular and epigenetic effects in breast carcinoma cells. Collectively, our data provide new insights into breast cancer prevention through epigenetic modulation of telomerase by using Pro-EGCG, a more stable form of EGCG, as a novel chemopreventive drug. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3206.
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) | 0,001 | 0,000 |
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 ».