PPARα-Selective Antagonist GW6471 Inhibits Cell Growth in Breast Cancer Stem Cells Inducing Energy Imbalance and Metabolic Stress

Biomedicines

Elisabetta Benedetti¹  Mariano Catanesi¹  Rodolfo Ippoliti¹  Vanessa Castelli¹  Francesca Lombardi¹  Annamaria Cimini¹  Michele d’Angelo¹  Margherita Alfonsetti¹  Benedetta Cinque¹  MariaGrazia Cifone¹  Chiara Laezza² 

[1] Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy;Institute of Endocrinology and Experimental Oncology G. Salvatore, CNR, 80131 Naples, Italy;

关键词: mammospheres;    CSCs;    metabolism;    spheroids;    triple-negative breast cancer;    MDA-MB-231;   

DOI  :  10.3390/biomedicines9020127

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown