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

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

Author information

1
Department of Molecular Biosciences, 1089 Veterinary Medicine Dr., VM3B, UC Davis, CA 95616, USA. Electronic address: sareveco@ucdavis.edu.
2
Department of Molecular Biosciences, 1089 Veterinary Medicine Dr., VM3B, UC Davis, CA 95616, USA. Electronic address: sddatta@ucdavis.edu.
3
Department of Molecular Biosciences, 1089 Veterinary Medicine Dr., VM3B, UC Davis, CA 95616, USA. Electronic address: jasandov@ucdavis.edu.
4
Department of Molecular Biosciences, 1089 Veterinary Medicine Dr., VM3B, UC Davis, CA 95616, USA. Electronic address: atomilov@ucdavis.edu.
5
Department of Pathology, Microbiology, and Immunology, 4206 Veterinary Medicine Dr., VM3A, UC Davis, CA 95616, USA. Electronic address: tksears@ucdavis.edu.
6
Department of Pathology, Microbiology, and Immunology, 4206 Veterinary Medicine Dr., VM3A, UC Davis, CA 95616, USA. Electronic address: kdwoolard@ucdavis.edu.
7
Department of Molecular Biosciences, 1089 Veterinary Medicine Dr., VM3B, UC Davis, CA 95616, USA. Electronic address: jmangelastro@ucdavis.edu.
8
Department of Molecular Biosciences, 1089 Veterinary Medicine Dr., VM3B, UC Davis, CA 95616, USA. Electronic address: gcortopassi@ucdavis.edu.

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

PMID:
31654752
DOI:
10.1016/j.mito.2019.09.009

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