PPARα-Selective Antagonist GW6471 Inhibits Cell Growth in Breast Cancer Stem Cells Inducing Energy Imbalance and Metabolic Stress.
CSCs
MDA-MB-231
mammospheres
metabolism
spheroids
triple-negative breast cancer
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
28 Jan 2021
28 Jan 2021
Historique:
received:
07
01
2021
revised:
24
01
2021
accepted:
26
01
2021
entrez:
2
2
2021
pubmed:
3
2
2021
medline:
3
2
2021
Statut:
epublish
Résumé
Breast cancer is the most frequent cancer and the second leading cause of death among women. Triple-negative breast cancer is the most aggressive subtype of breast cancer and is characterized by the absence of hormone receptors and human epithelial growth factor receptor 2. Cancer stem cells (CSCs) represent a small population of tumor cells showing a crucial role in tumor progression, metastasis, recurrence, and drug resistance. The presence of CSCs can explain the failure of conventional therapies to completely eradicate cancer. Thus, to overcome this limit, targeting CSCs may constitute a promising approach for breast cancer treatment, especially in the triple-negative form. To this purpose, we isolated and characterized breast cancer stem cells from a triple-negative breast cancer cell line, MDA-MB-231. The obtained mammospheres were then treated with the specific PPARα antagonist GW6471, after which, glucose, lipid metabolism, and invasiveness were analyzed. Notably, GW6471 reduced cancer stem cell viability, proliferation, and spheroid formation, leading to apoptosis and metabolic impairment. Overall, our findings suggest that GW6471 may be used as a potent adjuvant for gold standard therapies for triple-negative breast cancer, opening the possibility for preclinical and clinical trials for this class of compounds.
Identifiants
pubmed: 33525605
pii: biomedicines9020127
doi: 10.3390/biomedicines9020127
pmc: PMC7912302
pii:
doi:
Types de publication
Journal Article
Langues
eng
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