Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration.

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.

• Authors: Qing-hui Meng, Li-xin Zhou, Jia-lin Luo, Jian-ping Cao, Jian Tong, Sai-jun Fan
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 26 Issue 4 Pg. 492-9 (Apr 2005) ISSN: 1671-4083 [Print] United States
• PMID: 15780200 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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