Abstract 4215: Apoptosis induction in breast cancer cell lines by the dietary flavonoid fisetin
Notice bibliographique
Résumé
Abstract Canadian women have a lifetime probability of diagnosis of breast cancer of approximately 1 in 9. Although the current management of breast cancer is effective, significant morbidity and mortality are associated with the disease and its treatments. Fisetin, a phytochemical present in many fruits and vegetables, has demonstrated anticancer activity for both prostate and colon cancer. This study explores fisetin as a possible novel therapeutic modality for breast cancer. Breast cancer cell lines (MDA-MB-468, MDA-MB-231, MCF-7, T47-D, SKBR-3; mitozantrone-resistant (MITX) and paclitaxel-resistant (Tx400) cell lines) were exposed to fisetin and cell survival was assessed by MTT, crystal violet, acid phosphatase, and colony-forming assays. Normal cells (human mammary epithelial cells, fibroblasts, human umbilical vein endothelial cells) were used as negative controls. The mechanism of action of fisetin was explored using cell cycle analysis and assays for apoptosis/necrosis, including Annexin V-propidium iodide staining, DNA fragmentation measured by JAM assay, and LDH-release assay. Apoptosis induction pathways were studied using Western blotting, as well as caspase inhibitors and cell viability assays. Flow cytometry was used to assess mitochondrial membrane stability (DiOC6 staining) and reactive oxygen species (ROS) production (dihydroethidium staining). Fisetin exhibited a dose- and time-dependent cytotoxic effect on breast cancer cell lines (e.g., 100 µM fisetin decreased MDA-MB-468 cell viability by 70% at 72h in both crystal violet and acid phosphatase assays). In contrast, the viability of normal cells was not substantially affected by concentrations of fisetin that killed breast cancer cells. Fisetin-treated breast cancer cells showed cell cycle arrest (MDA-MB-468 cells arrested at G2/M phase; MDA-MB-231 cells arrested in S-phase) and death by apoptosis (e.g., MDA-MB-468 cells showed up to 50% apoptosis and 8% late apoptosis/necrosis by Annexin V-staining; cell cycle analysis and LDH-release assays supported these results). Fisetin-induced apoptosis was associated with mitochondrial membrane permeabilization but did not involve caspase activation since Western blotting showed that caspase-3 was not cleaved in fisetin-treated breast cancer cells and cell viability was not preserved in the presence of a pan-caspase inhibitor. In addition, fisetin did not cause ROS production in MDA-MB-468 or 231 cells, indicating that ROS do not contribute to the cytotoxic effect of fisetin. Together, these findings suggest that fisetin may be useful in the treatment of breast cancer. Ongoing studies are using Zebra fish as a model to explore the in vivo anticancer activity of fisetin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4215. doi:10.1158/1538-7445.AM2011-4215
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,010 | 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 tête enseignante, 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 ».