A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells

Maureen E. Lane, Bo Yu, Richard G. Pestell, Scott Wadler, Audie Rice, Kenneth E. Lipson, Chris Liang, Li Sun, Cho Tang, Gerald McMahon

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Recent studies have indicated that the development of cyclin-dependent kinase (cdk)2 inhibitors that deregulate E2F are a plausible pharmacological strategy for novel antineoplastic agents. We show here that 3-[1-(3H-Imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1, 3-dihydro-indol-2-one (SU9516), a novel 3-substituted indolinone compound, binds to and selectively inhibits the activity of cdk2. This inhibition results in a time-dependent decrease (4-64%) in the phosphorylation of the retinoblastoma protein pRb, an increase in caspase-3 activation (5-84%), and alterations in cell cycle resulting in either a G0-G1 or a G2-M block. We also report here cell line differences in the cdk-dependent phosphorylation of pRb. These findings demonstrate that SU9516 is a selective cdk2 inhibitor and support the theory that compounds that inhibit cdk2 are viable resources in the development of new antineoplastic agents.

Original languageEnglish (US)
Pages (from-to)6170-6177
Number of pages8
JournalCancer Research
Volume61
Issue number16
StatePublished - Aug 15 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells'. Together they form a unique fingerprint.

  • Cite this

    Lane, M. E., Yu, B., Pestell, R. G., Wadler, S., Rice, A., Lipson, K. E., Liang, C., Sun, L., Tang, C., & McMahon, G. (2001). A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells. Cancer Research, 61(16), 6170-6177.