The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression

  • Authors:
    • H. B. Liu
    • M. T. Voso
    • D. Gumiero
    • J. Duong
    • J. J. McKendrick
    • A. E. Dear
  • View Affiliations

  • Published online on: February 1, 2009     https://doi.org/10.3892/ijo_00000183
  • Pages: 573-579
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Abstract

A combination of demethylating agents and histone deacetylase inhibitors (HDACi) has been proposed as a novel therapy in leukemia and myelodysplasia. In HL-60 cells azacytidine (AZA) and Metacept-1 (MCT-1), a novel HDACi augmented inhibition of cell growth and increased apoptosis. In identifying a molecular mechanism responsible for these effects MCT-1 alone and in combination with AZA induced p15INK4b, p21WAF1/CIP1 and Caspase-3 whilst attenuating Bcl-XL expression. Interestingly, MCT-1 in combination with AZA significantly induced the recently identified suppressor of leukemogenesis Nur77 and attenuated AZA-induced MMP-9 expression. The combination of MCT-1 and AZA is more effective in inhibiting leukemic cell growth and induction of apoptosis. Regulation of a recently identified tumour suppressor gene together with cell cycle, apoptosis and matrix degrading proteases may underpin the molecular mechanism responsible for these effects.

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February 2009
Volume 34 Issue 2

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

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APA
Liu, H.B., Voso, M.T., Gumiero, D., Duong, J., McKendrick, J.J., & Dear, A.E. (2009). The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression. International Journal of Oncology, 34, 573-579. https://doi.org/10.3892/ijo_00000183
MLA
Liu, H. B., Voso, M. T., Gumiero, D., Duong, J., McKendrick, J. J., Dear, A. E."The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression". International Journal of Oncology 34.2 (2009): 573-579.
Chicago
Liu, H. B., Voso, M. T., Gumiero, D., Duong, J., McKendrick, J. J., Dear, A. E."The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression". International Journal of Oncology 34, no. 2 (2009): 573-579. https://doi.org/10.3892/ijo_00000183