Juglone induces GSDME axis pyroptosis in osteosarcoma cells via the JNK/P38 MAPK pathway

Jierui Zhao1, Xingyu Zhao2, Yue Lu2,3

  • 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, 999078, China.

Scientific Reports
|June 23, 2026
PubMed

Insights

Juglone induces pyroptosis, a programmed cell death, in osteosarcoma cells by activating the caspase-3/GSDME and JNK/p38 pathways. This suggests juglone

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • The MAPK signaling pathway is crucial for cancer inhibition.
  • Pyroptosis, a form of programmed cell death (PCD), impacts cancer progression.
  • Juglone inhibits cancer cell viability and motility, but its role in pyroptosis is unknown.

Purpose of the Study:

  • To investigate the in vitro effects of juglone on osteosarcoma (OS) cells.
  • To determine if juglone induces pyroptosis in OS cells.
  • To elucidate the regulatory mechanisms of juglone-induced pyroptosis.

Main Methods:

  • In vitro experiments on osteosarcoma cells.
  • Analysis of the caspase-3/GSDME pathway.
  • Investigation of the JNK/p38 signaling pathway.

Main Results:

  • Juglone was found to induce pyroptosis in OS cells.
  • The caspase-3/GSDME pathway mediates juglone-induced pyroptosis.
  • Juglone regulates the GSDME pathway via the JNK/p38 pathway, inducing both pyroptosis and apoptosis.

Conclusions:

  • Juglone effectively induces pyroptosis in osteosarcoma cells.
  • The caspase-3/GSDME and JNK/p38 pathways are key in juglone's mechanism.
  • Juglone shows potential as a therapeutic agent for osteosarcoma.

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