Oroxylin A induces G2/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2/p34 in human gastric carcinoma BGC-823 cells

J Pharm Pharmacol. 2008 Nov;60(11):1459-63. doi: 10.1211/jpp/60.11.0006.

Abstract

We reported previously that oroxylin A, a natural product isolated from Scutellariae Radix, was a potent apoptosis inducer of human hepatoma HepG2 cells. In this study, cell-cycle arrest of BGC-823 human gastric carcinoma cells caused by oroxylin A has been investigated. Based on our 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay and flow cytometric analysis, treatment of BGC-823 cells with growth suppressive concentrations of oroxylin A caused an irreversible arrest in the G2/M phase of the cell cycle. Western blot analysis demonstrated that oroxylin A-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in cdc2/p34, cyclin B1 and cyclin A expression. In addition, oroxylin A-treated cells decreased the expression of Cdk7, which was responsible for the low expression of M phase promoting factor (cyclin B1/Cdc2). The results suggested that oroxylin A induced G2/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2/p34 in human gastric carcinoma BGC-823 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Blotting, Western
  • CDC2 Protein Kinase / drug effects*
  • CDC2 Protein Kinase / metabolism
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cyclin A / drug effects
  • Cyclin A / metabolism
  • Cyclin B / drug effects
  • Cyclin B / metabolism
  • Cyclin B1
  • Cyclin-Dependent Kinase-Activating Kinase
  • Cyclin-Dependent Kinases / drug effects
  • Cyclin-Dependent Kinases / metabolism
  • Flavonoids / pharmacology*
  • Flow Cytometry
  • G2 Phase / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / pathology
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Antineoplastic Agents, Phytogenic
  • CCNB1 protein, human
  • Cyclin A
  • Cyclin B
  • Cyclin B1
  • Flavonoids
  • Tetrazolium Salts
  • Thiazoles
  • 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinases
  • thiazolyl blue
  • Cyclin-Dependent Kinase-Activating Kinase
  • CDK7 protein, human