Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 107, Issue -, Pages 1294-1301Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.08.063
Keywords
Sevoflurane; Volatile anesthetics; Wnt/beta-catenin; Stem/progenitors; Leukemia
Funding
- Shenzhen Medical University [8661213]
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Most of the studies regarding the direct effect of anesthetics on tumour cells are focused on opioids and voltage-gated sodium channels. Little is known on the effect of volatile anesthetics on tumour progression. In this study, we show that sevoflurane, a volatile anesthetic, negatively affects chronic myeloid leukemia (CML) CD34 stem/progenitor cells' biological properties. Sevoflurane significantly inhibits the growth of a panel of CML cell lines in a dose-dependent manner without affecting their survival. It also inhibits proliferation, differentiation and self-renewal capacities but not survival of CML CD34 cells. In addition, sevoflurane significantly augments dasatinib's efficacy in CML cell lines and stem/progenitors. Mechanistically, sevoflurane dose-dependently decreases levels of beta-catenin and c-Myc but not phospho-P38 MAPK in K562 and CML CD34 cells. The decreased Wnt/beta-catenin activity and the reduced levels of Wnt/beta-catenin-targeted transcriptions are observed in CML cells exposed to sevoflurane. The complete rescue of the inhibitory effects of sevoflurane in K562 and CML CD34 cells by beta-catenin stabilization using both genetic and pharmacological approaches further demonstrates that sevoflurane acts on CML cells via a beta-catenin-dependent manner. Our results clearly show the direct and negative effects of sevoflurane on the leukemia cell lines as well as leukemia stem/progenitors. Our findings also reveal Wnt/beta-catenin as the target of volatile anesthetics.
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