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

S. Abe, T. Kubota, Y. Otani, T. Furukawa, M. Watanabe, K. Kumai, M. Kitajima

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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.

Original languageEnglish
Pages (from-to)1260-1266
Number of pages7
JournalGan to kagaku ryoho. Cancer & chemotherapy
Volume27
Issue number8
Publication statusPublished - 2000 Jul
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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