GL331-induced disruption of cyclin B1/CDC 2 complex and inhibition of CDC 2 kinase activity

T. S. Huang, W. K. Yang, J. Whang-Peng

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

GL331, a new homologue of etoposide (VP-16), was developed to cope with the multiple drug resistance occurring in certain malignant tumours. We previously indicated that GL331, like VP-16 and other major cancer chemotherapeutic agents, induced apoptosis in a variety of human cancer cell lines including nasopharyngeal carcinoma (MPC) NPC-TW01 and NPC-TW04 cells. In this study, we further explored the effect of GL331 on the cell cycle progression of NPC cells. Flow cytometric analysis of DNA content was first used to demonstrate the ability of GL331 to induce cell growth arrest at 8-62 phase in most NPC cells. Besides acting as a topoisomerase II inhibitor, GL331 inhibited cellular cyclin B1-associated CDC 2 kinase activity 6 h after treatment, accounting partly at least for its induction of the cell cycle arrest. As with cyclin A, D1, E, CDK 2 and PCNA, the levels of cyclin B1 and CDC 2 proteins were not changed after GL331 treatment; however, the ability to form complex between cyclin B1 and CDC 2 was obviously affected in GL331-treated NPC cells, which associates with the inhibition of cyclin B1/CDC 2 kinase activity elicited by GL331. These data could provide more principal bases for future therapeutic application of this potential anti-cancer agent.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalApoptosis
Volume1
Issue number3
DOIs
Publication statusPublished - Dec 1 1996
Externally publishedYes

Keywords

  • CDC 2
  • Cell cycle
  • Cyclin b1
  • Etoposide (vp-16)
  • GL331

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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