Glaucocalyxin A induces apoptosis and autophagy in tongue squamous cell carcinoma cells by regulating ROS

Cancer Chemother Pharmacol. 2021 Aug;88(2):235-246. doi: 10.1007/s00280-021-04285-3. Epub 2021 Apr 27.

Abstract

Purpose: Tongue squamous cell carcinoma (TSCC) is the most common highly invasive oral cancer. Glaucocalyxin A (GLA) is a diterpenoid component isolated from Rabdosia japonica var. with anti-bacterial and anti-cancer biological properties. However, the role of GLA in human TSCC remains uncertain. The aim of this paper was to investigate the anti-cancer effect of GLA on TSCC cells as well as its underlying mechanism.

Methods: Cell viability and growth were analyzed by CCK-8 assay and colony formation, respectively. DAPI staining and flow cytometry assay were used to detect the cell apoptosis. Lysotracker Red staining was used to observe the lysosomes and autolysosomes of TSCC cells. ROS fluorescent probe was used to test the intracellular ROS levels. Western blotting was used to detect the expression levels of apoptosis- and autophagy-related proteins.

Results: GLA inhibits the cell viability and growth in TSCC cells. GLA induces TSCC cells apoptosis, autophagy and ROS production in a time- and concentration-dependent manner. In addition, GLA inhibits the viability of TSCC cells by inducing intracellular ROS production. Finally, GLA triggers ROS-dependent apoptosis and autophagy in TSCC cells.

Conclusion: Our results consistently suggested that GLA can induce apoptosis and autophagy in TSCC cells by generating ROS. GLA may serve as a promising therapeutic drug for overcoming TSCC.

Keywords: Apoptosis; Autophagy; Glaucocalyxin A; Reactive oxygen species; Tongue squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Diterpenes, Kaurane / pharmacology*
  • Humans
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Tongue / drug effects
  • Tongue / metabolism
  • Tongue Neoplasms / drug therapy*
  • Tongue Neoplasms / metabolism

Substances

  • Diterpenes, Kaurane
  • Reactive Oxygen Species
  • glaucocalyxin A