Abstract B23: Citral reduces ALDH1A3 activity in breast cancer: Potential applications in targeting breast cancer stem cells
Notice bibliographique
Résumé
Abstract Breast tumors contain a subpopulation of cells known as cancer stem cells (CSCs) which are highly tumorigenic, resistant to typical chemo- and radiotherapy, and express high levels of aldehyde dehydrogenase (ALDH) isoforms ALDH1A3 and ALDH1A1. These enzymes initiate retinoic acid (RA) signaling and potentially contribute to detoxification of chemotherapy. A compound that inhibits these enzymes could be used as an adjuvant therapy to target breast CSCs and/or re-sensitize this population to chemotherapy. In particular, there are no currently characterized inhibitors of the ALDH1A3 isoform, so twelve general ALDH inhibitors were tested for their effectiveness in targeting ALDH1A3 activity. Ability to directly inhibit ALDH activity was quantified with the Aldefluor assay on a patient tumor xenograft and on breast cancer cell lines MDA-MB-231, MDA-MB-468, and SKBR3. Inhibition of RA signaling was quantified by measuring RA-inducible gene expression after 24 hours treatment with ALDH inhibitor. To investigate the anti-cancer properties of these compounds, apoptosis was quantified with the annexin V assay after 24 hours treatment. To determine if increased ALDH1A3 expression is involved in chemoresistance, MDA-MB-231 cells overexpressing ALDH1A3 and MDA-MB-468 cells with ALDH1A3 shRNA knockdown were treated for 72 hours with doxorubicin, 4-hydroperoxycyclophosphamide, or paclitaxel. Increased ALDH1A3 expression did not affect the amount of chemotherapy-induced apoptosis or cell proliferation rates. Citral significantly reduced ALDH1A3-mediated expression of RA-inducible genes and significantly reduced the ALDH activity of the patient-derived xenograft as well as ALDH1A3-overexpression MDA-MB-231 cells. Citral induced apoptosis in an ALDH1A3-dependant manner in breast cancer cell lines, and its ability to reduce MDA-MB-231 in vivo growth was investigated by implanting MDA-MB-231 cells in female NOD/SCID mice and injecting with 0.1mg/kg citral. Tumor size was not affected by citral injections, however recent data suggests that micelle-encapsulated citral has the potential to reduce tumor bulk. Should citral prove to be an effective breast cancer and ALDH1A3 inhibitor in future tumor xenograft experiments, this compound could potentially be used as adjuvant therapy for breast cancer patients. Citation Format: Margaret L. Thomas, Krysta M. Coyle, Brianne Cruickshank, Michael Giacomantonio, Melissa Wallace, Carman Giacomantonio, Paola Marcato. Citral reduces ALDH1A3 activity in breast cancer: Potential applications in targeting breast cancer stem cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr B23.
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 | 0,001 | 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 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 ».