Kaempferol suppresses proliferation and induces apoptosis and DNA damage in human gallbladder cancer cells through the CDK4/CDK6/cyclin D1 pathway

Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1311-1321. doi: 10.26355/eurrev_202102_24836.

Abstract

Objective: Kaempferol has been reported to play an anti-tumor role in various human cancers, while its role in gallbladder cancer (GBC) is unclear.

Materials and methods: We found that kaempferol significantly inhibited the growth, invasion and migration, meanwhile induced apoptosis through cells arrested at G0/G1 phase of GBC cell lines, including GBC-SD and SGC996 cells in vitro.

Results: Kaempferol promoted the release of cytochrome C from the mitochondria to cytoplasm, the activation of c-caspase-3 and c-caspase-9 and increased the expression levels of pro-apoptotic factor Bax, meanwhile decreased the expression levels of anti-apoptotic factor Bcl-2. In addition, the expression levels of CDK4, CDK6 and cyclin D1, which are members of the CDK4/CDK6/cyclin D1 signaling pathway, were also decreased by kaempferol. Moreover, kaempferol could efficiently prevent tumor progression of GBC in the xenograft in vivo.

Conclusions: Our results demonstrated that kaempferol suppressed GBC progression through activation of the CDK4/CDK6/cyclin D1 signaling pathway, suggesting that it might be a potential anti-tumor agent for clinical treatment of GBC.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Cyclin D1 / antagonists & inhibitors*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism
  • DNA Damage
  • Drug Screening Assays, Antitumor
  • Female
  • Gallbladder Neoplasms / drug therapy*
  • Gallbladder Neoplasms / metabolism
  • Gallbladder Neoplasms / pathology
  • Humans
  • Kaempferols / chemistry
  • Kaempferols / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • CCND1 protein, human
  • Kaempferols
  • Cyclin D1
  • kaempferol
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6