Platyphyllenone Induces Autophagy and Apoptosis by Modulating the AKT and JNK Mitogen-Activated Protein Kinase Pathways in Oral Cancer Cells

Int J Mol Sci. 2021 Apr 19;22(8):4211. doi: 10.3390/ijms22084211.

Abstract

Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.

Keywords: apoptosis; autophagy; oral; platyphyllenone.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Blotting, Western
  • Caspase 3
  • Caspase 8 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Ketones / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mouth Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Ketones
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8