Sinapine induced ferroptosis in non-small cell lung cancer cells by upregulating transferrin/transferrin receptor and downregulating SLC7A11

Gene. 2022 Jun 15:827:146460. doi: 10.1016/j.gene.2022.146460. Epub 2022 Mar 28.

Abstract

Sinapine (SI) is a naturally occurring product with biological properties, but its activity against non-small cell lung cancer (NSCLC) remains unclear. This research examined the anti-tumour effects of SI in NSCLC cells and the underlying mechanisms of any effects. SI induced ferroptosis, a novel form of cell death, by increasing intracellular ferrous iron, lipid peroxidation, and reactive oxygen species (ROS) in NSCLC cells. SI treatment resulted in transferrin and transferrin receptor upregulation, and inhibition of transferrin or the transferrin receptor reduced the ferroptosis caused by SI. SI treatment also resulted in a p-53 dependent downregulation of SLC7A11. Finally, we evaluated the effects of SI in vivo and it was found that SI also successfully inhibited the growth of NSCLC in vivo. In summary, our data demonstrated that SI triggered ferroptosis in NSCLC cells and may be a promising therapeutic agent for this condition.

Keywords: Ferroptosis; Non-small cell lung cancer; Sinapine; p53.

MeSH terms

  • Amino Acid Transport System y+ / genetics
  • Amino Acid Transport System y+ / metabolism
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Choline / analogs & derivatives
  • Ferroptosis*
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Receptors, Transferrin / genetics
  • Receptors, Transferrin / therapeutic use
  • Transferrin

Substances

  • Amino Acid Transport System y+
  • Receptors, Transferrin
  • SLC7A11 protein, human
  • Transferrin
  • sinapine
  • Choline