Shikonin Induces Autophagy and Apoptosis in Esophageal Cancer EC9706 Cells by Regulating the AMPK/mTOR/ULK Axis

Anal Cell Pathol (Amst). 2024 Oct 29:2024:7752299. doi: 10.1155/2024/7752299. eCollection 2024.

Abstract

Shikonin is a plant medicine extracted from Lithospermum, which dominate influential antioxidant and antitumor effect. Here, we report that shikonin was capable of inducing human esophageal cancer EC9706 cell apoptosis and autophagy, in a time- and dose-dependent manner. Shikonin exposure repressed cell viability and migration and invasion capabilities and caused EC9706 cell autophagy and apoptosis by activating the AMPK/mTOR/ULK axis. Autophagy inhibition secured EC9706 cells against shikonin-induced autophagy and apoptosis and reversed the upregulation of AMPK and ULK phosphorylation and downregulation of mTOR phosphorylation provoked by shikonin. In summary, shikonin instigates EC9706 cell apoptosis and autophagy using the target AMPK/mTOR/ULK signal pathway axis, which provides a potential new target to treat human esophageal cancer.

Keywords: apoptosis; autophagy; esophageal cancer; shikonin; the AMPK/mTOR/ULK axis.

MeSH terms

  • AMP-Activated Protein Kinases* / metabolism
  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Autophagy-Related Protein-1 Homolog / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / pathology
  • Humans
  • Naphthoquinones* / pharmacology
  • Phosphorylation / drug effects
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • shikonin
  • Naphthoquinones
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • MTOR protein, human
  • Autophagy-Related Protein-1 Homolog