Bypassing the Δ6‐desaturase enzyme and directly providing n‐3 and n‐6 PUFA pathway intermediates reduces the survival of two human breast cancer cell lines
Notice bibliographique
Résumé
The n‐3 long chain polyunsaturated fatty acids (PUFA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acid, and in some studies, the n‐6 long chain PUFA arachidonic acid (AA), inhibit survival of breast cancer cells in vitro and in vivo. Less is known about the intermediates synthesized from the dietary 18 carbon fatty acids. The objective of this study was to determine the survival and phospholipid (PL) fatty acid composition of tumorigenic (MDA‐MB‐231, MCF‐7) and non‐tumorigenic (MCF‐12A) breast cells treated with intermediates in the n‐3 and n‐6 pathway. N‐3 intermediates, stearidonic acid (SDA) and eicosatetraenoic acid (ETA), and n‐6 intermediates, γ‐linolenic acid (GLA) and dihomo γ‐linolenic acid (DGLA), reduced ( P < 0.05) the growth of tumorigenic but not MCF‐12A cells. All treatments resulted in a higher PUFA and saturated content and a lower monounsaturated content in tumorigenic cells ( P < 0.05). For MDA‐MB‐231 PL, treatment with SDA and ETA increased ETA, EPA, and docosapentaenoic acid (DPA) and lowered AA, while treatment with GLA and DGLA primarily increased DGLA with only a small decrease in the DPA and DHA ( P < 0.05). For MCF‐7 PL, due to low desaturase activity, the n‐3 intermediates increased ETA and the n‐6 increased DGLA ( P < 0.05). Our findings suggest that the less studied n‐6 (GLA and DGLA) and n‐3 (SDA and ETA) fatty acids could serve as alternative dietary sources of bioactive lipids targeted at breast cancer. Practical applications: There is a growing body of literature suggesting that consumption of EPA and DHA can prevent and extend the life of the millions of women affected with breast cancer. This research explored the effect of treatment with fatty acid intermediates on the lipid composition and survival of human breast cancer cell lines. These intermediates bypass the rate limiting enzymes involved in desaturation of the dietary essential fatty acids. We provide evidence in vitro in two well‐established human breast cancer cell lines that providing intermediates in the n‐3 and n‐6 PUFA pathways reduce the survival of tumor cells. The resulting fatty acid composition of tumor phospholipids suggests that the mechanism of these fatty acids is unlikely due to increasing the content of the 20 and 22 carbon PUFA in the membrane. As few dietary sources of these intermediates exist, this study provides a rational to explore the development of novel animal and plant sources for their anti‐cancer activity. Further work is needed in animal models using patient derived xenographs to confirm that these changes occur in vivo. Providing MDA‐MB‐231, MCF‐7, and MCF‐12A cells with n‐3 and n‐6 pathway intermediates after the Δ6 desaturase reduced growth of the two tumor cell lines and resulted in elongation of the intermediate fatty acids. Δ5 de‐saturation of fatty acids occurred in the n‐3 pathway.
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 | 0,004 | 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 | 0,001 | 0,003 |
| 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) | 0,000 | 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 ».