Apoptosis

, Volume 2, Issue 5, pp 463–470

Cell cycle G2/M arrest and activation of cyclin-dependent kinases associated with low-dose paclitaxel-induced sub-G1 apoptosis

  • C.-H. Shu
  • W. K. Yang
  • Y.-L. Shih
  • M.-L. Kuo
  • T.-S. Huang
Article
  • 1k Downloads

Abstract

Paclitaxel is a potential anti-cancer agent for several malignancies including ovary, breast, and head and neck cancers. This study investigated the kinetics of paclitaxel-induced cell cycle perturbation in two human nasopharyngeal carcinoma (NPC) cell lines, NPC-TW01 and NPC-TW04. NPC cells treated with higher concentrations (0.1 or 1 µM) of paclitaxel showed obvious G2/M arrest and then converted to a cell population with reduced DNA content, which was detected as a sub-G2 peak in the flow cytometric histographs. If a low concentration (5 nM) of paclitaxel was used instead, transient G2/M arrest was observed in NPC cells, which subsequently converted to a sub-G1 form during the treatment period. Internucleosomal fragmentation and chromatin condensation were detectable in these sub-G1 and sub-G2 cells, suggesting that persistent or transient G2/M arrest is a prerequisite step for apoptosis elicited by varying doses of paclitaxel. The levels of cyclins A, B1, D1, E, CDK 1 (CDC 2), CDK 2 and proliferating cell nuclear antigen (PCNA) were unchanged in NPC cells following treatment with any concentration of paclitaxel; however, apoptosis-related cyclin B1-associated CDC 2 kinase was highly activated by paclitaxel even at concentrations as low as 5 nM, which is consistent with the finding that low-dose paclitaxel is also able to induce apoptosis in NPC cells. Activation of cyclin B1-associated CDC 2 kinase seems to be an important G2/M event required for paclitaxel-induced apoptosis, and this activation of cyclin B1/CDC 2 kinase could be attributed to the increased activity of CDK 7 kinase.

Apoptosis CDC 2 (CDK 1) CDK 7 cyclin B1 G2/M arrest paclitaxel (Taxol(tm)) 

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Copyright information

© Chapman and Hall 1997

Authors and Affiliations

  • C.-H. Shu
    • 1
  • W. K. Yang
    • 2
  • Y.-L. Shih
    • 2
  • M.-L. Kuo
    • 3
  • T.-S. Huang
    • 2
  1. 1.Department of Otolaryngology, Veterans General Hospital (VGH)-Taipei and Institute of Clinical Medicine, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  2. 2.Cooperative Laboratory at VGH-Taipei, Cancer Research DivisionNational Health Research InstitutesTaipeiTaiwan
  3. 3.Institute of ToxicologyNational Taiwan UniversityTaipeiTaiwan

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