Kaempferol Induces G2/M Cell Cycle Arrest via Checkpoint Kinase 2 and Promotes Apoptosis via Death Receptors in Human Ovarian Carcinoma A2780/CP70 Cells

Molecules. 2018 May 5;23(5):1095. doi: 10.3390/molecules23051095.

Abstract

Kaempferol is a widely distributed dietary flavonoid. Epidemiological studies have demonstrated kaempferol consumption lowers the risk of ovarian cancer. Our previous research proved that kaempferol suppresses human ovarian cancer cells by inhibiting tumor angiogenesis. However, the effects of kaempferol on the cell cycle and extrinsic apoptosis of ovarian cancer cells have not yet been studied. In the present study, we demonstrated that kaempferol induced G2/M cell cycle arrest via the Chk2/Cdc25C/Cdc2 pathway and Chk2/p21/Cdc2 pathway in human ovarian cancer A2780/CP70 cells. Chk2 was not responsible for kaempferol-induced apoptosis and up-regulation of p53. Kaempferol stimulated extrinsic apoptosis via death receptors/FADD/Caspase-8 pathway. Our study suggested that Chk2 and death receptors played important roles in the anticancer activity of kaempferol in A2780/CP70 cells. These findings provide more evidence of the anti-ovarian cancer properties of kaempferol and suggest that kaempferol could be a potential candidate for ovarian cancer adjuvant therapy.

Keywords: Chk2; DR5; Fas; apoptosis; cell cycle arrest; kaempferol.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Checkpoint Kinase 2 / genetics*
  • Checkpoint Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Fas-Associated Death Domain Protein / genetics
  • Fas-Associated Death Domain Protein / metabolism
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaempferols / pharmacology*
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Receptors, Death Domain / genetics*
  • Receptors, Death Domain / metabolism
  • Signal Transduction
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Cyclin-Dependent Kinase Inhibitor p21
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Kaempferols
  • Receptors, Death Domain
  • kaempferol
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • CDC25C protein, human
  • cdc25 Phosphatases
  • CASP8 protein, human
  • Caspase 8