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

S. Abe, T. Kubota, Y. Otani, Toshiharu 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
JournalJapanese Journal of Cancer and Chemotherapy
Volume27
Issue number8
Publication statusPublished - 2000 Jul
Externally publishedYes

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Phosphotransferases
Heterografts
Cell Line
Neoplasms
Growth
Pancreatic Neoplasms
Nude Mice
7-hydroxystaurosporine
Appointments and Schedules
Proteins
Breast Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

Abe, S., Kubota, T., Otani, Y., Furukawa, T., Watanabe, M., Kumai, K., & Kitajima, M. (2000). Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21. Japanese Journal of Cancer and Chemotherapy, 27(8), 1260-1266.

Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21. / Abe, S.; Kubota, T.; Otani, Y.; Furukawa, Toshiharu; Watanabe, M.; Kumai, K.; Kitajima, M.

In: Japanese Journal of Cancer and Chemotherapy, Vol. 27, No. 8, 07.2000, p. 1260-1266.

Research output: Contribution to journalArticle

Abe, S, Kubota, T, Otani, Y, Furukawa, T, Watanabe, M, Kumai, K & Kitajima, M 2000, 'Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21', Japanese Journal of Cancer and Chemotherapy, vol. 27, no. 8, pp. 1260-1266.
Abe S, Kubota T, Otani Y, Furukawa T, Watanabe M, Kumai K et al. Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21. Japanese Journal of Cancer and Chemotherapy. 2000 Jul;27(8):1260-1266.
Abe, S. ; Kubota, T. ; Otani, Y. ; Furukawa, Toshiharu ; Watanabe, M. ; Kumai, K. ; Kitajima, M. / Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21. In: Japanese Journal of Cancer and Chemotherapy. 2000 ; Vol. 27, No. 8. pp. 1260-1266.
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AB - 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.

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