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5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells

Abstract : 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.
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Submitted on : Wednesday, September 29, 2021 - 12:13:50 PM
Last modification on : Friday, March 11, 2022 - 6:14:02 PM
Long-term archiving on: : Thursday, December 30, 2021 - 7:01:36 PM

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

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