Tumorigenic effect mediated by ROS/eicosanoids and their regulation on TP53 expression in a murine mammary gland adenocarcinoma

Prostaglandins Other Lipid Mediat. 2021 Aug:155:106564. doi: 10.1016/j.prostaglandins.2021.106564. Epub 2021 May 15.

Abstract

The aim of this study was to investigate the in vivo and in vitro effects of dietary ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) and their derivatives on the expression of TP53 and their relationship with cellular proliferation and death in a murine mammary adenocarcinoma model. BALB/c mice were divided in three diet groups: chia oil (ChO) rich in ω-3, corn oil (CO) rich in ω-6/ω-3 and safflower oil (SO) rich in ω-6 and subcutaneously inoculated with LMM3 mammary tumor cell line. Results demonstrated that diets with higher concentration of omega-6 PUFAs induced an increment of linoleic and arachidonic acid on tumor cell membranes increasing ROS liberation, 12(S)-HHT generation, TP53, Ki67 expression and cell proliferation. However, diets enriched with high content in omega-3 PUFAs induced higher tumor cell apoptosis and tumor infiltration of CD3+ lymphocytes, lowest cell viability and proliferation. Dietary omega-3 PUFAs nutritional intervention can be used as a potential preventative strategy to inhibit the molecular signaling pathways involved in the mammary tumor growth process as the TP53.

Keywords: Dietary PUFAs; Eicosanoids; Mammary cancer; ROS; TP53.

MeSH terms

  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / pathology
  • Animals
  • Apoptosis / drug effects
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-3 / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C*
  • Reactive Oxygen Species* / metabolism
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Reactive Oxygen Species
  • Fatty Acids, Omega-3
  • Trp53 protein, mouse