A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia

  • Authors:
    • M. Sumi
    • T. Tauchi
    • G. Sashida
    • A. Nakajima
    • A. Gotoh
    • K. Shin-Ya
    • J. H. Ohyashiki
    • K. Ohyashiki
  • View Affiliations

  • Published online on: June 1, 2004     https://doi.org/10.3892/ijo.24.6.1481
  • Pages: 1481-1487
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Abstract

Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is up-regulated in the vast majority of human neoplasias but not in normal somatic tissues. Therefore, the telomerase complex represents a promising universal therapeutic target in cancer. Telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to inhibit telomerase activity. We examined G-quadruplex interactive agent, telomestatin (SOT-095), for its ability to inhibit the proliferation of human leukemia cells, including freshly obtained leukemia cells. Telomere length was determined by either the terminal restriction fragment method or flow-FISH, and apoptosis was assessed by flow cytometry. Moreover, chemosensitivity was examined in telomestatin-treated U937 cells before ultimate telomere shortening. Treatment with telomestatin reproducibly inhibited telomerase activity in U937 and NB4 cells followed by telomere shortening. Enhanced chemosensitivity toward daunorubicin and cytosine-arabinoside was observed in telomestatin-treated U937 cells, before ultimate telomere shortening. Telomere shortening associated with apoptosis by telomestatin was evident in some freshly obtained leukemia cells from acute myeloid leukemia patients, regardless of sub-types of AML and post-myelodysplasia AML. These results suggest that disruption of telomere maintenance by telomestatin limits the cellular lifespan of AML cells, as well. However, in a minority of AML patients apoptosis was not evident, thus indicating that resistant mechanism might exist in some freshly obtained AML cells. Therefore, further investigation of telomestatin as a therapeutic agent is warranted.

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June 2004
Volume 24 Issue 6

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

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Spandidos Publications style
Sumi M, Tauchi T, Sashida G, Nakajima A, Gotoh A, Shin-Ya K, Ohyashiki JH and Ohyashiki K: A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia. Int J Oncol 24: 1481-1487, 2004
APA
Sumi, M., Tauchi, T., Sashida, G., Nakajima, A., Gotoh, A., Shin-Ya, K. ... Ohyashiki, K. (2004). A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia. International Journal of Oncology, 24, 1481-1487. https://doi.org/10.3892/ijo.24.6.1481
MLA
Sumi, M., Tauchi, T., Sashida, G., Nakajima, A., Gotoh, A., Shin-Ya, K., Ohyashiki, J. H., Ohyashiki, K."A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia". International Journal of Oncology 24.6 (2004): 1481-1487.
Chicago
Sumi, M., Tauchi, T., Sashida, G., Nakajima, A., Gotoh, A., Shin-Ya, K., Ohyashiki, J. H., Ohyashiki, K."A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia". International Journal of Oncology 24, no. 6 (2004): 1481-1487. https://doi.org/10.3892/ijo.24.6.1481