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Volatile anesthetics sevoflurane targets leukemia stem/progenitor cells via Wnt/β-catenin inhibition

Xuguang Ruan1, Weihang Jiang1, Pingrui Cheng1

  • 1Department of Anesthesiology, Panyu Central Hospital, Guangzhou, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|September 28, 2018
PubMed

Insights

Sevoflurane, a volatile anesthetic, inhibits chronic myeloid leukemia (CML) cell growth and stem cell properties. It enhances dasatinib efficacy by targeting the Wnt/β-catenin pathway.

Area of Science:

  • Oncology
  • Anesthesiology
  • Molecular Biology

Background:

  • Limited research exists on volatile anesthetics' impact on tumor progression.
  • Opioids and sodium channels are the primary focus regarding anesthetics and tumor cells.

Purpose of the Study:

  • To investigate the direct effects of sevoflurane on chronic myeloid leukemia (CML) cells.
  • To elucidate the mechanisms underlying sevoflurane's action on CML stem/progenitor cells.

Main Methods:

  • Dose-dependent assays on CML cell lines and CD34+ stem/progenitor cells.
  • Analysis of cell proliferation, differentiation, self-renewal, and survival.
  • Western blotting for key signaling molecules (β-catenin, c-Myc, phospho-P38 MAPK).
  • Assessment of Wnt/β-catenin pathway activity and targeted gene expression.
  • Rescue experiments using genetic and pharmacological β-catenin stabilization.

Main Results:

  • Sevoflurane inhibited CML cell line growth and CML CD34+ stem/progenitor cell proliferation, differentiation, and self-renewal without affecting survival.
  • Sevoflurane significantly enhanced the efficacy of dasatinib in CML cells.
  • Mechanistically, sevoflurane decreased β-catenin and c-Myc levels, reducing Wnt/β-catenin pathway activity.
  • Stabilization of β-catenin rescued the inhibitory effects of sevoflurane, confirming a β-catenin-dependent mechanism.

Conclusions:

  • Sevoflurane exerts direct, negative effects on leukemia cell lines and stem/progenitor cells.
  • The Wnt/β-catenin pathway is identified as a key target for sevoflurane's action in CML.
  • Findings suggest potential therapeutic implications for sevoflurane in CML treatment, particularly in combination with targeted therapies.
Keywords:
LeukemiaSevofluraneStem/progenitorsVolatile anestheticsWnt/β-catenin

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