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  • Title: Volatile anesthetics sevoflurane targets leukemia stem/progenitor cells via Wnt/β-catenin inhibition.
    Author: Ruan X, Jiang W, Cheng P, Huang L, Li X, He Y, Mai M, Tan Z.
    Journal: Biomed Pharmacother; 2018 Nov; 107():1294-1301. PubMed ID: 30257344.
    Abstract:
    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 β-catenin and c-Myc but not phospho-P38 MAPK in K562 and CML CD34 cells. The decreased Wnt/ β-catenin activity and the reduced levels of Wnt/β-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 β-catenin stabilization using both genetic and pharmacological approaches further demonstrates that sevoflurane acts on CML cells via a β-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/β-catenin as the target of volatile anesthetics.
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