[Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21].

Abstract

Five human cancer cell lines (MKN 45, HT-29, WiDr, PAN-3-JCK, and CRL 1420) were used to evaluate the antitumor spectrum of UCN-01, which suppressed the growth of these digestive cancer cell lines. A human pancreatic cancer xenograft (CRL 1420) and breast cancer xenograft (MX-1) were used to determine their sensitivity to UCN-01, in nude mice. UCN-01 significantly suppressed the tumor growth of CRL 1420 at a dose of 10 mg/kg in a schedule of (qd x 5) x 2, but was ineffective for MX-1. While p21 protein expression was induced by UCN-01 in both CRL 1420 and MX-1, an accumulation of dephosphorylated ppRb was observed only in CRL 1420, resulting in G1 block as detected by flow cytometric analysis. The CDK 2 activity of MX-1 was almost 6 times higher than that of CRL 1420, which might account for the resistance of MX-1 to UCN-01 in spite of the induction of p21 in this strain. We conclude that the determinant of sensitivity to UCN-01 lies in the balance of CDK 2 kinase activity and p21 protein induction.

• Authors: S Abe, T Kubota, Y Otani, T Furukawa, M Watanabe, K Kumai, M Kitajima
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 27 Issue 8 Pg. 1260-6 (Jul 2000) ISSN: 0385-0684 [Print] Japan
• PMID: 10945025 (Publication Type: Journal Article)

Chemical References

• Alkaloids
• 7-hydroxystaurosporine
• Protein Serine-Threonine Kinases
• CDC2-CDC28 Kinases
• Cdk2 protein, mouse
• Cyclin-Dependent Kinase 2
• Cyclin-Dependent Kinases
• Staurosporine

Topics

• Alkaloids (pharmacology)
• Animals
• CDC2-CDC28 Kinases
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Cyclin-Dependent Kinase 2
• Cyclin-Dependent Kinases (metabolism)
• Drug Screening Assays, Antitumor
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Protein Serine-Threonine Kinases (metabolism)
• Signal Transduction
• Staurosporine (analogs & derivatives)
• Tumor Cells, Cultured (drug effects)