Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration

Acta Pharmacol Sin. 2005 Apr;26(4):492-9. doi: 10.1111/j.1745-7254.2005.00087.x.

Abstract

Aim: To investigate the effect of 7-hydroxystaurosporine (UCN-01), a selective protein kinase C (PKC) inhibitor, on cell growth, migration, and invasion in invasive human glioblastoma U-87MG cells.

Methods: PKC activity was determined based on the PKC-catalyzed transfer of the (32)P-phosphate group from [g-(32)P]ATP into a PKC-specific peptide substrate. Cell viability was measured by MTT assay. Cell invasion and migration were evaluated by a Boyden chamber assay and scratch wound assay, respectively. Protein expression was analyzed using Western blot assay. The formation of 3-dimensional cellular aggregates was examined by a cell-cell aggregation assay.

Results: UCN-01 treatment resulted in concentration- and time-dependent inhibition of U-87MG cell growth at higher doses (>100 nmol/L), and reduced cell invasion and migration capability at less cytotoxic doses (<100 nmol/L). UCN-01 significantly repressed PKC activity. Consistent with this result, UCN-01 blocked cell invasion stimulated by phorbel 12-myristate-13-acetate (PMA) and ethanol (EtOH), 2 PKC activators. Enforced expression of the tumor suppressor genes BRCA1 and PTEN increased the anti-invasion potential of UCN-01. Exposure to UCN-01 caused a dose-dependent increase in cell adhesion molecule E-cadherin. The effect of UCN-01 on the formation of cell-cell aggregation was significantly reduced by the addition of an anti-E-cadherin antibody.

Conclusion: UCN-01 inhibits the invasion and migration of human glioma cells. Accordingly, UCN-01 can have potential clinical applications for the treatment of human glioma metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • BRCA1 Protein / metabolism
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Glioblastoma / enzymology
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Staurosporine / analogs & derivatives*
  • Staurosporine / pharmacology

Substances

  • BRCA1 Protein
  • Cadherins
  • RNA, Messenger
  • 7-hydroxystaurosporine
  • Protein Kinase C
  • Staurosporine