Multimodal antiproliferative effects of oleanolic acid mitocans: In vitro and in vivo studies

Puerta, Adrián ; González-Bakker, Aday ; Romanos, Eduardo ; Domínguez, Inmaculada Aguilar ; Martínez-Montiel, Mónica ; Merino-Montiel, Penélope ; Pérez Herrera, Raquel ; Gimeno Floría, M. Concepción ; Fernández-Bolaños, José G. ; López, Óscar ; Padrón, José M.

Resumen: Mitochondria-targeting drugs (mitocans) based on organic cations are emerging as powerful and selective cancer therapeutics. In this study, we have evaluated a novel series of oleanolic acid-derived mitocans, revealing nanomolar-range antiproliferative effects against human solid tumor cells. Continuous live-cell imaging revealed extensive cytoplasmic vacuolation, while mechanistic studies identified paraptosis as the dominant form of cell death. Remarkably, in vivo experiments demonstrated significant tumor growth inhibition in mice, with no detectable toxicity at therapeutic doses. These findings highlight the potential of oleanolic acid-derived mitocans as promising candidates for cancer therapy.

Idioma: Inglés

DOI: 10.1016/j.bcp.2025.116807

Año: 2025

Publicado en: Biochemical Pharmacology 234 (2025), 116807 [16 pp.]
ISSN: 0006-2952

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2020-116460RB-I00
Financiación: info:eu-repo/grantAgreement/ES/DGA/E07-23R
Financiación: info:eu-repo/grantAgreement/ES/AEI/MICNN/PID2021-123059OB-I00

Tipo y forma: Artículo (Versión definitiva)