Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK/ERK signaling pathway

  • Authors:
    • Lei Shi
    • Xiang-Qin Weng
    • Yan Sheng
    • Jing Wu
    • Ming Ding
    • Xun Cai
  • View Affiliations

  • Published online on: September 23, 2016     https://doi.org/10.3892/or.2016.5123
  • Pages: 3072-3080
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Abstract

Although all-trans retinoic acid (ATRA) is regarded as a prominent example of differentiation therapy, it is not effective for the treatment of other subtypes of acute myeloid leukemia (AML) beyond acute promyelocytic leukemia (APL). Therefore, new strategies need to be explored to extend the efficacy of ATRA-based therapy to non-APL AML patients. In the present study, staurosporine, a protein kinase C (PKC) pan-inhibitor, exhibited synergism with ATRA to promote granulocytic differentiation in poorly ATRA-sensitive U937 cells but not in ATRA unresponsive K562 and Kasumi cells. Staurosporine or the combined treatment did not affect PKC activity in U937 cells. Moreover, other selective PKC inhibitors, UCN-01, Go6976 or rottlerin failed to enhance ATRA‑induced granulocytic differentiation in U937 cells. Therefore, staurosporine-enhanced ATRA-induced granulocytic differentiation in U937 cells may be independent of PKC. Staurosporine activated mitogen‑activated protein kinase kinase (MEK) and extracellular signal‑regulated kinase (ERK). Meanwhile, staurosporine also enhanced ATRA-promoted upregulation of the protein level of CCAAT/enhancer‑binding protein β (C/EBPβ) and C/EBPε in U937 cells. Furthermore, blockade of MEK activation suppressed staurosporine‑enhanced differentiation as well as the elevated protein level of C/EBPs. Taken together, we concluded that staurosporine enhanced ATRA‑induced granulocytic differentiation in U937 cells via MEK/ERK-mediated modulation of the protein level of C/EBPs.
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November-2016
Volume 36 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Shi L, Weng X, Sheng Y, Wu J, Ding M and Cai X: Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK/ERK signaling pathway. Oncol Rep 36: 3072-3080, 2016.
APA
Shi, L., Weng, X., Sheng, Y., Wu, J., Ding, M., & Cai, X. (2016). Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK/ERK signaling pathway. Oncology Reports, 36, 3072-3080. https://doi.org/10.3892/or.2016.5123
MLA
Shi, L., Weng, X., Sheng, Y., Wu, J., Ding, M., Cai, X."Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK/ERK signaling pathway". Oncology Reports 36.5 (2016): 3072-3080.
Chicago
Shi, L., Weng, X., Sheng, Y., Wu, J., Ding, M., Cai, X."Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK/ERK signaling pathway". Oncology Reports 36, no. 5 (2016): 3072-3080. https://doi.org/10.3892/or.2016.5123