ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

Cell Biol Int. 2020 Nov;44(11):2334-2343. doi: 10.1002/cbin.11443. Epub 2020 Aug 22.

Abstract

Colorectal cancer (CRC) is one of the most pressing health issues in today's society. As such, it is imperative that the scientific community devise effective methods to inhibit the proliferation and metastasis of CRC cells. Ferroptosis is a recently discovered regulatory cell death mode mainly manifested by dysregulation of cellular iron metabolism and mitochondrial lipid peroxidation. ACADSB is a member of the acyl-CoA dehydrogenase. This study finds that ACADSB is lowly expressed in CRC tissues. Its expression is negatively correlated with N- and M-stage CRC but positively correlated with the overall survival rate of CRC patients. In addition, it finds that ACADSB is found in the mitochondria of cells. Overexpression of ACADSB inhibits CRC cell migration, invasion, and proliferation, while ACADSB knockdown has the opposite effect. More importantly, the study finds that ACADSB negatively regulates expression of glutathione reductase and glutathione peroxidase 4, the two main enzymes responsible for clearing glutathione (GSH) in CRC cells. ACADSB overexpression enhances the concentration of malondialdehyde, Fe+ , superoxide dismutase, and lipid peroxidation in CRC cells, but reduces the concentration of GSH. This is significant, as all of these are important indicators of ferroptosis. Evaluating the data as a whole, this paper speculates that ACADSB affects CRC cell migration, invasion, and proliferation by regulating CRC cell ferroptosis.

Keywords: cancer; cell death; cell migration; enzymes; metabolism; tumor suppressor.

MeSH terms

  • Acyl-CoA Dehydrogenase / genetics
  • Acyl-CoA Dehydrogenase / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • China
  • Colorectal Neoplasms / metabolism*
  • Databases, Genetic
  • Ferroptosis / physiology*
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness / genetics

Substances

  • Acyl-CoA Dehydrogenase