Microtubule inhibitor D-24851 induces p53-independent apoptotic cell death in malignant glioma cells through Bcl-2 phosphorylation and Bax translocation

  • Authors:
    • Hideaki Ito
    • Takao Kanzawa
    • Seiji Kondo
    • Yasuko Kondo
  • View Affiliations

  • Published online on: March 1, 2005     https://doi.org/10.3892/ijo.26.3.589
  • Pages: 589-596
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Abstract

D-24851 is a recently developed microtubule inhibitor that induces G2/M cell-cycle arrest and has an antitumor effect in many cancer cell types. It is expected to be a promising chemotherapeutic agent against a broad range of tumors. However, the precise mechanisms underlying its antitumor effect remain to be determined. Here, we investigated the in vitro effect of D-24851 on tumor growth and the apoptosis mechanism in human malignant glioma cells. Because both p53-dependent and -independent pathways of apoptosis have been reported, we used cell lines with wild-type p53 (U87-MG and D54) and cell lines with mutant p53 (U373-MG and T98G) and compared their responses to D-24851. D-24851 substantially inhibited the proliferation of the four glioma cell lines tested in a dose- and time-dependent manner. The inhibitory effect of D-24851 on tumor growth was associated with cell-cycle arrest in G2/M, subsequently inducing apoptosis. D-24851 treatment induced phosphorylated Bcl-2 and translocated Bax from the cytoplasm to the mitochondria, resulting in apoptotic cell death. These events took place regardless of the p53 status of tumor cells. Our results indicated that D-24851 effectively induces apoptosis through Bcl-2 phosphorylation and Bax translocation in human malignant glioma cells in a p53-independent manner. The results of this study make D-24851 even more promising as a therapeutic agent, especially because many malignant gliomas have a heterogeneous p53 status.

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March 2005
Volume 26 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Ito, H., Kanzawa, T., Kondo, S., & Kondo, Y. (2005). Microtubule inhibitor D-24851 induces p53-independent apoptotic cell death in malignant glioma cells through Bcl-2 phosphorylation and Bax translocation. International Journal of Oncology, 26, 589-596. https://doi.org/10.3892/ijo.26.3.589
MLA
Ito, H., Kanzawa, T., Kondo, S., Kondo, Y."Microtubule inhibitor D-24851 induces p53-independent apoptotic cell death in malignant glioma cells through Bcl-2 phosphorylation and Bax translocation". International Journal of Oncology 26.3 (2005): 589-596.
Chicago
Ito, H., Kanzawa, T., Kondo, S., Kondo, Y."Microtubule inhibitor D-24851 induces p53-independent apoptotic cell death in malignant glioma cells through Bcl-2 phosphorylation and Bax translocation". International Journal of Oncology 26, no. 3 (2005): 589-596. https://doi.org/10.3892/ijo.26.3.589