Open Access5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells
Author(s) -
Oumaima Jaouadi,
Inès Limam,
Mohamed Abdelkarim,
Emna Berred,
Ahlem Chahbi,
Mélody Caillot,
Brigitte Sola,
Fatma Ben Aissa-Fennira
Publication year - 2021
Publication title -
cancers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.818
H-Index - 76
ISSN - 2072-6694
DOI - 10.3390/cancers13153747
Subject(s) - multiple myeloma , apoptosis , viability assay , chemistry , cancer research , in vivo , in vitro , oxidative stress , autophagy , cell culture , pharmacology , biology , biochemistry , immunology , genetics
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.