Squalene in Nanoparticles Improves Antiproliferative Effect on Human Colon Carcinoma Cells Through Apoptosis by Disturbances in Redox Balance

Bidooki, Seyed Hesamoddin ; Quero, Javier (Universidad de Zaragoza) ; Sánchez-Marco, Javier ; Herrero-Continente, Tania ; Marmol, Inés ; Lasheras, Roberto ; Sebastian, Victor (Universidad de Zaragoza) ; Arruebo, Manuel (Universidad de Zaragoza) ; Osada, Jesús (Universidad de Zaragoza) ; Rodriguez-Yoldi, María Jesús (Universidad de Zaragoza)

Resumen: Squalene, a triterpene found in extra virgin olive oil, has therapeutic properties in diseases related to oxidative stress, such as cancer. However, its hydrophobic nature and susceptibility to oxidation limit its bioavailability outside of olive oil. To expand its applications, alternative delivery methods are necessary. The objective of the present study was to examine the impact of squalene encapsulated in PLGA (poly(lactic-co-glycolic) acid) nanoparticles (PLGA + Sq) on the proliferation of human colon carcinoma Caco-2 cells, as well as its underlying mechanism of action. The findings demonstrated that PLGA + Sq exert no influence on differentiated cells; however, it is capable of reducing the proliferation of undifferentiated Caco-2 cells through apoptosis and cell cycle arrest in the G1 phase. This effect was initiated by the release of cytochrome c into the cytoplasm and the subsequent activation of caspase-3. Furthermore, squalene exhibited pro-oxidant activity, as evidenced by an increase in intracellular ROS (reactive oxygen species) levels. The results of the squalene effect on genes associated with cell death, inflammation, and the cell cycle indicate that its antiproliferative effect may be post-transcriptional. In conclusion, PLGA + Sq demonstrate an antiproliferative effect on Caco-2 cells through apoptosis by altering redox balance, suggesting squalene’s potential as a functional food ingredient for colorectal cancer prevention.

Idioma: Inglés

DOI: 10.3390/ijms252313048

Año: 2024

Publicado en: International Journal of Molecular Sciences 25, 23 (2024), 13048 [17 pp.]
ISSN: 1661-6596

Financiación: info:eu-repo/grantAgreement/ES/DGA/B16-23R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-1364140B- I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PRTR-C17.I1
Financiación: info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG/NEWPOWER-S1-1.1-E01116

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)