The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer - 13/01/23
Abstract |
Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
The Graphical Abstract was partly generated using Servier Medical Art (provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license), and using assets from Freepik.com.
The Graphical Abstract was partly generated using Servier Medical Art (provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license), and using assets from Freepik.com.ga1Le texte complet de cet article est disponible en PDF.
Highlights |
• | Stauprimide inhibits cell growth in TNBC cells inducing cell cycle arrest in G2/M. |
• | Stauprimide reduces migratory potential of TNBC cells. |
• | PI3K/Akt, ERK1/2 and p38-MAPK pathways are modulated by stauprimide in TNBC cells. |
• | MYC expression is inhibited by stauprimide in TNBC cells. |
• | Stauprimide impairs tumor viability and metastasis in orthotopic models of TNBC. |
Keywords : Stauprimide, Triple-negative breast cancer, Antitumoral compound, Proliferation, Migration
Plan
Vol 158
Article 114070- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?