Cetylpyridinium chloride is a potent AMP-activated kinase (AMPK) inducer and has therapeutic potential in cancer

Mitochondrion. 2020 Jan;50:19-24. doi: 10.1016/j.mito.2019.09.009. Epub 2019 Oct 22.

Abstract

AMP-activated protein kinase (AMPK) is a eukaryotic energy sensor and protector from mitochondrial/energetic stress that is also a therapeutic target for cancer and metabolic disease. Metformin is an AMPK inducer that has been used in cancer therapeutic trials. Through screening we isolated cetylpyridinium chloride (CPC), a drug known to dose-dependently inhibit mitochondrial complex 1, as a potent and dose-dependent AMPK stimulator. Mitochondrial biogenesis and bioenergetics changes have also been implicated in glioblastoma, which is the most aggressive form of brain tumors. Cetylpyridinium chloride has been administered in humans as a safe drug-disinfectant for several decades, and we report here that under in vitro conditions, cetylpyridinium chloride kills glioblastoma cells in a dose dependent manner at a higher efficacy compared to current standard of care drug, temozolomide.

Keywords: AMP-activated protein kinase; AMPK; Cancer; Cetylpyridinium chloride; Mitochondrial inhibitor; Quaternary ammonium salt.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism*
  • Animals
  • Anti-Infective Agents, Local / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Survival
  • Cetylpyridinium / pharmacology*
  • Glioma / drug therapy
  • Hepatocytes / drug effects*
  • Humans
  • Mice
  • Neoplastic Stem Cells / drug effects*

Substances

  • Anti-Infective Agents, Local
  • Antineoplastic Agents
  • Cetylpyridinium
  • Adenylate Kinase