2024-03-28T09:53:16Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1670262022-10-19T07:54:11Zcom_10261_81com_10261_5col_10261_334
Bort Bueno, Alicia
Quesada Sánchez, Sergio
Ramos-Torres, Ágata
Gargantilla, Marta
Priego, Eva María
Raynal, S.
Lepifre, F.
Gasalla, José María
Rodriguez-Henche, Nieves
Castro, Ana
Díaz-Laviada, Inés
2018-06-26T11:40:45Z
2018-06-26T11:40:45Z
2018
Scientific Reports 8 (2018)
http://hdl.handle.net/10261/167026
10.1038/s41598-018-22690-2
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100010805
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.13039/501100010198
http://dx.doi.org/10.13039/501100011698
29531259
The key metabolic sensor adenosine monophosphate-dependent kinase (AMPK) has emerged as a promising therapeutic target for cancer prevention and treatment. Besides its role in energy homeostasis, AMPK blocks cell cycle, regulates autophagy and suppresses the anabolic processes required for rapid cell growth. AMPK is especially relevant in prostate cancer in which activation of lipogenic pathways correlate with tumor progression and aggressiveness. This study reports the discovery of a new series of 2-oxindole derivatives whose AMPK modulatory ability, as well as the antitumoral profile in prostate cancer cells, was evaluated. One of the assayed compounds, compound 8c, notably activated AMPK in cultured PC-3, DU145 and LNCaP prostate cancer cells. Likewise, compound 8c caused PC-3, DU145 and LNCaP cells viability inhibition. Selective knocking down of α1 or α2 isoforms as well as in vitro assays using human recombinant α1β1γ1 or α2β1γ1 AMPK isoforms revealed that compound 8c exhibit preference for AMPKα1. Consistent with efficacy at the cellular level, compound 8c was potent in suppressing the growth of PC-3 xenograft tumors. In conclusion, our results show that a new 2-oxindole fluorinated derivative exerts potent in vivo antitumor actions against prostate cancer cells, indicating a promising clinical therapeutic strategy for the treatment of androgen-independent prostate cancer.
eng
openAccess
Identification of a novel 2-oxindole fluorinated derivative as in vivo antitumor agent for prostate cancer acting via AMPK activation
artículo