Mechanism of Juglone-Induced Cell Cycle Arrest and Apoptosis in Ishikawa Human Endometrial Cancer Cells

J Agric Food Chem. 2019 Jul 3;67(26):7378-7389. doi: 10.1021/acs.jafc.9b02759. Epub 2019 Jun 25.


The molecular mechanism of Juglone-induced cell cycle arrest and apoptosis in human endometrial cancer cells was investigated. Juglone was purified from the green husk of Carya cathayensis Sarg and identified by HPLC, LC-MS/MS, and NMR. At an IC50 of 20.81 μM, juglone significantly inhibited Ishikawa cell proliferation, as shown by S phase arrest mediated by inactivation of cyclin A protein ( p < 0.05). The ROS levels increased significantly after exposure to juglone, which paralleled increases in the mRNA and protein expression of p21 and decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A. The expression of Bcl-2 and Bcl-xL was significantly down-regulated, whereas the expression of Bax, Bad and cyto c was up-regulated, and we later confirmed the involvement of the mitochondrial pathway in juglone-induced apoptosis. Our in vitro results stated that juglone can be studied further as an effective natural anticancer agent.

Keywords: Sarg; Ishikawa; apoptosis; cell cycle; juglone; reactive oxygen species.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Carya / chemistry*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / physiopathology*
  • Female
  • Humans
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism


  • Antineoplastic Agents, Phytogenic
  • Naphthoquinones
  • Plant Extracts
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • CDC25A protein, human
  • cdc25 Phosphatases
  • juglone