Myoglobin mutant with enhanced nitrite reductase activity regulates intracellular oxidative stress in human breast cancer cells

Arch Biochem Biophys. 2022 Nov 15:730:109399. doi: 10.1016/j.abb.2022.109399. Epub 2022 Sep 15.

Abstract

Heme proteins play vital roles in regulating the reactive oxygen/nitrogen species (ROS/RNS) levels in cells. In this study, we overexpressed human wild-type (WT) myoglobin (Mb) and its double mutant, F43H/H64A Mb with enhanced nitrite reductase (NIR) activity, in the typical representative triple-negative breast cancer cell, MDA-MB-231 cells. The results showed that the overexpression of F43H/H64A Mb increased the level of nitric oxide (NO) and the degree of oxidative stress, and then activated Akt/MAPK mediated apoptotic cascade, whereas WT Mb showed the opposite effect. This study indicates that Mb plays an important role in maintaining the balance of the cellular redox system and could thus be a valuable target for cancer therapy.

Keywords: Breast cancer; Myoglobin; Nitric oxide; Nitrite reductase; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • Female
  • Humans
  • Myoglobin* / genetics
  • Myoglobin* / metabolism
  • Nitric Oxide / metabolism
  • Nitrite Reductases / genetics
  • Nitrite Reductases / metabolism
  • Nitrites / metabolism
  • Nitrogen
  • Oxidative Stress
  • Oxygen / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species

Substances

  • Myoglobin
  • Nitric Oxide
  • Nitrites
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-akt
  • Oxygen
  • Nitrite Reductases
  • Nitrogen