Multimodal antiproliferative effects of oleanolic acid mitocans: In vitro and in vivo studies
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.
Authors
- Raquel P. Herrera (ORCID: https://orcid.org/0000-0002-5244-9569)
- José Manuel Padrón (ORCID: https://orcid.org/0000-0001-6268-6552)
- Aday González‐Bakker (ORCID: https://orcid.org/0000-0002-9792-5194)
- Penélope Merino‐Montiel (ORCID: https://orcid.org/0000-0003-1376-9671)
- José G. Fernández‐Bolaños (ORCID: https://orcid.org/0000-0003-1499-0650)
- Adrián Puerta
- Mónica Martínez-Montiel
- M. Concepción Gimeno (ORCID: https://orcid.org/0000-0003-0553-0695)
- Oscar L. López (ORCID: https://orcid.org/0000-0002-8546-8256)
- Eduardo Romanos
- Isabel Domínguez (ORCID: https://orcid.org/0009-0002-6000-0734)
Institutions
- Universidad de La Laguna (ES)
- Universidad de Zaragoza (ES)
- Instituto de Síntesis Química y Catálisis Homogénea (ES)
- Benemérita Universidad Autónoma de Puebla (MX)
- Universidad de Sevilla (ES)
Publication Details
- Journal
- Biochemical Pharmacology
- Published
- 2025-02-18
- DOI
- https://doi.org/10.1016/j.bcp.2025.116807
- Citations
- 2
- Primary Topic
- Natural product bioactivities and synthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Ministerio de Ciencia e Innovación