Gossypol Inhibits Metastasis of Lung Cell Carcinoma by Reversing Epithelial to Mesenchymal Transition and Suppressing Proteases Activity

Environ Toxicol. 2024 Nov;39(11):5209-5221. doi: 10.1002/tox.24363. Epub 2024 Sep 12.

Abstract

Gossypol, a natural polyphenolic compound, possesses antivirus activity and induces cell death of different types of tumors. However, the efficacy of gossypol on lung carcinoma metastases and epithelial to mesenchymal transition remains unknown. The aim of the present work was to determine the cellular and molecular mechanism of the anti-cancer and anti-metastatic efficacies of gossypol on human lung carcinoma cells. Gossypol showed a marked suppression of the viability, motility, and invasion in H1299 and A549 cells. Zymography assay showed that gossypol was sufficient to suppress the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2. Gossypol reversed TGF-β-induced epithelial to mesenchymal transition. Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice.

Keywords: epithelial to mesenchymal transition; gossypol; invasion; lung cancer; metastases.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Epithelial-Mesenchymal Transition* / drug effects
  • Gossypol* / analogs & derivatives
  • Gossypol* / pharmacology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / secondary
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Inbred BALB C*
  • Mice, Nude*
  • Mice, SCID
  • Peptide Hydrolases / metabolism
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Gossypol
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2
  • Peptide Hydrolases
  • Antineoplastic Agents