Abstract 2262: Anti-proliferative and cytotoxic activities of the anti-malarial compound artesunate for breast and ovarian cancer cell lines.
Notice bibliographique
Résumé
Abstract Introduction: In women, breast cancer is the most prevalent cancer diagnosis while ovarian cancer represents the most lethal gynecological neoplasm. Together, these cancer types place a huge burden on society, comprising 20% of all estimated cancer deaths in the USA for 2012. The high incidence and mortality rates of these cancer types, in addition to the emergence of multi-drug resistant variants, highlights the need to develop novel therapeutic agents with greater efficacy. Artesunate (ART) is a semi-synthetic derivative of artemisinin, a natural compound derived from the Chinese herb Artemisia annua L. ART is an antimalarial agent that also possesses potent anticancer activity. Since the use of ART as an antimalarial agent is associated with few adverse effects, ART may represent a less toxic alternative to conventional chemotherapy. This study investigates the cytotoxic effects of ART on breast and ovarian cancer cell lines and the mechanisms underlying its activity. Methods & Results: ART exhibited a dose- and time-dependent effect on a panel of breast and ovarian cancer cell lines. Anticancer activity was also observed in 3-D cultures of both cancer cell types. Oregon Green 488 and propidium iodide (PI) staining of cancer cells revealed that ART strongly inhibited cancer cell proliferation, arresting cells in the G1 or G2 phases of the cell cycle. ART-mediated G2 arrest was dependent on reactive oxygen species (ROS), as in the presence of an antioxidant all cell lines arrested in G1. ART's antiproliferative effect was due in part to its ability to modulate the expression of cell cycle regulatory proteins including cyclin D3, p21, CDK4 and CDC25C. Annexin V/PI staining of ART-treated cancer cells revealed that ART induced ROS-dependent apoptosis in both breast and ovarian cancer cell lines. Pretreatment of cancer cells with a pan-caspase inhibitor decreased but did not eliminate ART-induced cytotoxicity, suggesting that caspase-dependent apoptosis is one of several pathways involved in ART-mediated killing of cancer cells. ART caused ROS-dependent DNA damage indicated by the presence of γH2AX, which implicates the DNA damage pathway in ART-induced cancer cell death. Annexin V/PI staining of ART-treated normal dermal fibroblasts and human mammary epithelial cells demonstrated that ART had limited cytotoxicity for normal cells at doses that were toxic to cancer cells, highlighting an increased sensitivity of cancer cells to ART treatment. Conclusions: These data show that ART has a potent antiproliferative and cytotoxic effect on both breast and ovarian cancer cells with limited cytotoxicity for normal cells. ART's specific cytotoxic activity and excellent safety record in malaria patients make it a worthy candidate for further investigation as a possible treatment for breast and ovarian cancer. Supported by NSERC and the CBCF-Atlantic Region Citation Format: Anna L. Greenshields, David Hoskin. Anti-proliferative and cytotoxic activities of the anti-malarial compound artesunate for breast and ovarian cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2262. doi:10.1158/1538-7445.AM2013-2262
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) | 0,002 | 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 ».