Investigation of the content differences of arachidonic acid metabolites in a mouse model of breast cancer by using LC-MS/MS

J Pharm Biomed Anal. 2021 Feb 5:194:113763. doi: 10.1016/j.jpba.2020.113763. Epub 2020 Nov 20.

Abstract

Arachidonic acid (AA) is closely associated with breast cancer. In addition to the two metabolic pathways regulated by cyclooxygenase and lipoxygenase, AA has a third metabolic pathway through which cytochrome P450 (CYP) enzymes produce hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs). The targeted CYP-mediated pathway of AA can not only kill cancer cells but also inhibit the interstitial microenvironment around a tumor. Therefore, it makes sense to identify potential biomarkers from the AA metabolome for the diagnosis and treatment of breast cancer. This study established a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of AA and its main metabolites, EETs and HETEs, in MMTV-PyMT mice, a spontaneous breast cancer mouse model. The results showed that there were significant differences in the concentrations of AA, 12-HETE, 19-HETE and 8,9-EET in plasma and tumor tissues between normal and MMTV-PyMT mice. Therefore, the eicosanoids mentioned above may be used as new biomarkers for breast cancer diagnosis. This study provides a new perspective for the recognition and diagnosis of breast cancer.

Keywords: Arachidonic acid (AA); Biomarker; Breast cancer; Cytochrome P450; LC–MS/MS.

MeSH terms

  • Animals
  • Arachidonic Acid
  • Chromatography, Liquid
  • Cytochrome P-450 Enzyme System
  • Eicosanoids
  • Hydroxyeicosatetraenoic Acids
  • Mammary Neoplasms, Experimental
  • Mice
  • Neoplasms*
  • Tandem Mass Spectrometry*

Substances

  • Eicosanoids
  • Hydroxyeicosatetraenoic Acids
  • Arachidonic Acid
  • Cytochrome P-450 Enzyme System