5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells

Oumaima Jaoua (1) , Inès Lima (1) , Mohamed Abdelkarim (1) , Emna Berred (1, 2) , Ahlem Chahbi (1) , Mélody Caillot (3) , Brigitte Sola (3) , Fatma Ben Aissa-Fennira (1)

1 University of Tunis El Manar
2 Aziza Othmana Hospital [Tunis]
3 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques

Multiple myeloma (MM) is an incurable plasma cell malignancy with frequent patient relapse due to innate or acquired drug resistance. Cholesterol metabolism is reported to be altered in MM; therefore, we investigated the potential anti-myeloma activity of two cholesterol derivatives: the 5,6 α- and 5,6 β-epoxycholesterol (EC) isomers. To this end, viability assays were used, and isomers were shown to exhibit important anti-tumor activity in vitro in JJN3 and U266 human myeloma cell lines (HMCLs) and ex vivo in myeloma patients' sorted CD138+ malignant cells. Moreover, we confirmed that 5,6 α-EC and 5,6 β-EC induced oxiapoptophagy through concomitant oxidative stress and caspase-3-mediated apoptosis and autophagy. Interestingly, in combination treatment a synergistic interaction was observed between 5,6 α-EC and 5,6 β-EC on myeloma cells. These data highlight a striking anti-tumor activity of 5,6 α-EC and 5,6 β-EC bioactive molecules against human myeloma cells, paving the way for their potential role in future therapeutic strategies in MM.

Mots clés: anti-tumor activity; apoptosis; autophagy; multiple myeloma; oxiapotophagy; oxidative stress; oxysterols; synergistic interaction

Domaines: Organisation et fonctions cellulaires [q-bio.SC]; Interactions cellulaires [q-bio.CB]; Cancer

Oumaima Jaoua, Inès Lima, Mohamed Abdelkarim, Emna Berred, Ahlem Chahbi, et al.. 5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells. Cancers, 2021, 13 (15), pp.3747. ⟨10.3390/cancers13153747⟩. ⟨hal-03358345⟩