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Article

Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid

  • Authors:
    • Noriyoshi Iriyama
    • Bo Yuan
    • Yuta Yoshino
    • Yoshihiro Hatta
    • Akira Horikoshi
    • Shin Aizawa
    • Masami Takei
    • Jin Takeuchi
    • Norio Takagi
    • Hiroo Toyoda
  • View Affiliations / Copyright

    Affiliations: Department of Hematology and Rheumatology, Nihon University School of Medicine, Itabashi Hospital, Itabashi-ku, Tokyo 173-8610, Japan, Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan, Department of Functional Morphology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan, Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan
  • Pages: 865-873
    |
    Published online on: December 30, 2013
       https://doi.org/10.3892/ijo.2013.2236
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Abstract

The effects of all-trans retinoic acid (ATRA) and valproic acid (VPA), alone and in combination, on the human acute promyelocytic leukemia (APL) cell line NB4 were investigated in view of differentiation induction and growth inhibition. After 48 h of treatment, not only ATRA but also VPA induced differentiation in NB4 cells, and their combination further augmented the differentiation activity. Furthermore, the upregulation of transcription factors including CCAAT/enhancer-binding proteins (CEBPα, β, ε) and PU.1, which are known to be critical factors for normal myelopoiesis, granulocytic maturation and being repressed in APL, concurred with the differentiation induction. A significant cell growth inhibition was observed after the treatment with VPA, which was further strengthened by the addition of ATRA. Given the importance of C/EBPs and PU.1 in myeloid development, these results, thus, suggest that restoration of the normal function of the myeloid cell transcriptional machinery is a major molecular mechanism underlying the differentiation induction in NB4. Therefore, these results may provide novel insights into a possible combinational therapeutic approach for APL patients.
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Copy and paste a formatted citation
Spandidos Publications style
Iriyama N, Yuan B, Yoshino Y, Hatta Y, Horikoshi A, Aizawa S, Takei M, Takeuchi J, Takagi N, Toyoda H, Toyoda H, et al: Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid. Int J Oncol 44: 865-873, 2014.
APA
Iriyama, N., Yuan, B., Yoshino, Y., Hatta, Y., Horikoshi, A., Aizawa, S. ... Toyoda, H. (2014). Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid. International Journal of Oncology, 44, 865-873. https://doi.org/10.3892/ijo.2013.2236
MLA
Iriyama, N., Yuan, B., Yoshino, Y., Hatta, Y., Horikoshi, A., Aizawa, S., Takei, M., Takeuchi, J., Takagi, N., Toyoda, H."Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid". International Journal of Oncology 44.3 (2014): 865-873.
Chicago
Iriyama, N., Yuan, B., Yoshino, Y., Hatta, Y., Horikoshi, A., Aizawa, S., Takei, M., Takeuchi, J., Takagi, N., Toyoda, H."Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid". International Journal of Oncology 44, no. 3 (2014): 865-873. https://doi.org/10.3892/ijo.2013.2236
Copy and paste a formatted citation
x
Spandidos Publications style
Iriyama N, Yuan B, Yoshino Y, Hatta Y, Horikoshi A, Aizawa S, Takei M, Takeuchi J, Takagi N, Toyoda H, Toyoda H, et al: Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid. Int J Oncol 44: 865-873, 2014.
APA
Iriyama, N., Yuan, B., Yoshino, Y., Hatta, Y., Horikoshi, A., Aizawa, S. ... Toyoda, H. (2014). Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid. International Journal of Oncology, 44, 865-873. https://doi.org/10.3892/ijo.2013.2236
MLA
Iriyama, N., Yuan, B., Yoshino, Y., Hatta, Y., Horikoshi, A., Aizawa, S., Takei, M., Takeuchi, J., Takagi, N., Toyoda, H."Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid". International Journal of Oncology 44.3 (2014): 865-873.
Chicago
Iriyama, N., Yuan, B., Yoshino, Y., Hatta, Y., Horikoshi, A., Aizawa, S., Takei, M., Takeuchi, J., Takagi, N., Toyoda, H."Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid". International Journal of Oncology 44, no. 3 (2014): 865-873. https://doi.org/10.3892/ijo.2013.2236
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