Salarin C inhibits the maintenance of chronic myeloid leukemia progenitor cells

E. Del Poggetto, M. Tanturli, N. Ben-Califa, A. Gozzini, I. Tusa, G. Cheloni, I. Marzi, M. G. Cipolleschi, Y. Kashman, D. Neumann, E. Rovida, P. Dello Sbarba

Research output: Contribution to journalArticlepeer-review

Abstract

We previously showed that incubation of chronic myeloid leukemia (CML) cells in very low oxygen selects a cell subset where the oncogenetic BCR/Abl protein is suppressed and which is thereby refractory to tyrosine kinase inhibitors used for CML therapy. In this study, salarin C, an anticancer macrolide extracted from the Fascaplysinopsis sponge, was tested as for its activity on CML cells, especially after their incubation in atmosphere at 0.1% oxygen. Salarin C induced mitotic cycle arrest, apoptosis and DNA damage. Salarin C also concentration-dependently inhibited the maintenance of stem cell potential in cultures in low oxygen of either CML cell lines or primary cells. Surprisingly, the drug also concentration-dependently enforced the maintenance of BCR/Abl signaling in low oxygen, an effect which was paralleled by the rescue of sensitivity of stem cell potential to IM. These results suggest a potential use of salarin C for the suppression of CML cells refractory to tyrosine kinase inhibitors.

Original languageEnglish
Pages (from-to)3146-3154
Number of pages9
JournalCell Cycle
Volume14
Issue number19
DOIs
StatePublished - 2015

Keywords

  • CR/Abl suppression
  • Chronic Myeloid Leukemia
  • Drug-resistance
  • Hypoxia
  • Imatinib-mesylate
  • Leukemia stem cells
  • Tyrosine kinase inhibitors

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