Cancers (Jul 2021)

5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells

  • Oumaima Jaouadi,
  • Inès Limam,
  • Mohamed Abdelkarim,
  • Emna Berred,
  • Ahlem Chahbi,
  • Mélody Caillot,
  • Brigitte Sola,
  • Fatma Ben Aissa-Fennira

DOI
https://doi.org/10.3390/cancers13153747
Journal volume & issue
Vol. 13, no. 15
p. 3747

Abstract

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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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