Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation

  • Authors:
    • Dong Yeok Shin
    • You-Soo Park
    • Kwangmo Yang
    • Gi-Young Kim
    • Wun-Jae Kim
    • Min Ho Han
    • Ho Sung Kang
    • Yung Hyun Choi
  • View Affiliations

  • Published online on: July 5, 2012     https://doi.org/10.3892/ijo.2012.1546
  • Pages: 910-918
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Abstract

The DNA methyltransferase inhibitor decitabine, 5-aza-2'-deoxycytidine, has been found to exert anti-metabolic and anticancer activities when tested against various cultured cancer cells. Furthermore, decitabine has been found to play critical roles in cell cycle arrest and apoptosis in various cancer cell lines; however, these roles are not well understood. In this study, we investigated decitabine for its potential anti-proliferative and apoptotic effects in human leukemia cell lines U937 and HL60. Our results indicated that treatment with decitabine resulted in significantly inhibited cell growth in a concentration- and time-dependent manner by the induction of apoptosis. Decitabine-induced apoptosis in U937 and HL60 cells was correlated with the downregulation of anti-apoptotic Bcl-2, XIAP, cIAP-1 and cIAP-2 protein levels, the cleavage of Bid proteins, the activation of caspases and the collapse of mitochondrial membrane potential (MMP). However, apoptosis induced by decitabine was attenuated by caspase inhibitors, indicating an important role for caspases in decitabine responses. The data further demonstrated that decitabine increased intracellular reactive oxygen species (ROS) generation. Moreover, N-acetyl-L-cysteine, a widely used ROS scavenger, effectively blocked the decitabine-induced apoptotic effects via inhibition of ROS production and MMP collapse. These observations clearly indicate that decitabine-induced ROS in human leukemia cells are key mediators of MMP collapse, which leads to apoptosis induction followed by caspase activation.
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September 2012
Volume 41 Issue 3

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

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Spandidos Publications style
Shin DY, Park Y, Yang K, Kim G, Kim W, Han MH, Kang HS and Choi YH: Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation. Int J Oncol 41: 910-918, 2012
APA
Shin, D.Y., Park, Y., Yang, K., Kim, G., Kim, W., Han, M.H. ... Choi, Y.H. (2012). Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation. International Journal of Oncology, 41, 910-918. https://doi.org/10.3892/ijo.2012.1546
MLA
Shin, D. Y., Park, Y., Yang, K., Kim, G., Kim, W., Han, M. H., Kang, H. S., Choi, Y. H."Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation". International Journal of Oncology 41.3 (2012): 910-918.
Chicago
Shin, D. Y., Park, Y., Yang, K., Kim, G., Kim, W., Han, M. H., Kang, H. S., Choi, Y. H."Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation". International Journal of Oncology 41, no. 3 (2012): 910-918. https://doi.org/10.3892/ijo.2012.1546