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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Article

Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells

  • Authors:
    • Yingyu Chen
    • Jing Li
    • Jianda Hu
    • Jing Zheng
    • Zhihong Zheng
    • Tingbo Liu
    • Zhenxing Lin
    • Minhui Lin
  • View Affiliations / Copyright

    Affiliations: Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fuzhou 350001, Fujian, P.R. China
  • Pages: 2076-2084
    |
    Published online on: August 19, 2014
       https://doi.org/10.3892/ijo.2014.2610
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Abstract

Emodin, an extracted natural compound from the root and rhizome of Rheum palmatum L, has been shown to have multiple biological activities including anticancer functions in previous studies. In this study, we investigated the anti-leukemic activity of emodin alone or emodin in the presence all-trans retinoic acid (ATRA) in acute myeloid leukemia (AML) cells and the potential signaling pathway involved. We demonstrated that emodin could significantly enhance the sensitivity to ATRA and present additive differentiation-inducing effects in AML cell line NB4 cells and, especially, in NB4-derived ATRA-resistant MR2 cells. Further study showed that increasing dose of emodin could effectively induce growth inhibition and apoptotic effects in both cell lines as well as in primary leukemic cells from AML patients. Moreover, the apoptotic induction in AML cells was associated with the activation of caspase cascades involving caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage. In addition, leukemic cell response to emodin stimuli in vitro was observed through the decreased expression levels of Bcl-2 and retinoic acid receptor α (RARα). Importantly, emodin was demonstrated as a new inhibitor of PI3K/Akt in AML cells, even in primary AML cells. It inhibited Akt phosphoration (p-Akt) at Ser473 as efficiently as mTOR at Ser2448. Consistently, it exerted suppression effects on the phosphoration of mTOR downstream targets, 4E-BP1 and p70S6K. Taken together, these findings indicate that emodin might be developed as a promising anti-leukemic agent to improve the patient outcome in AML.
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Copy and paste a formatted citation
Spandidos Publications style
Chen Y, Li J, Hu J, Zheng J, Zheng Z, Liu T, Lin Z and Lin M: Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells. Int J Oncol 45: 2076-2084, 2014.
APA
Chen, Y., Li, J., Hu, J., Zheng, J., Zheng, Z., Liu, T. ... Lin, M. (2014). Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells. International Journal of Oncology, 45, 2076-2084. https://doi.org/10.3892/ijo.2014.2610
MLA
Chen, Y., Li, J., Hu, J., Zheng, J., Zheng, Z., Liu, T., Lin, Z., Lin, M."Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells". International Journal of Oncology 45.5 (2014): 2076-2084.
Chicago
Chen, Y., Li, J., Hu, J., Zheng, J., Zheng, Z., Liu, T., Lin, Z., Lin, M."Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells". International Journal of Oncology 45, no. 5 (2014): 2076-2084. https://doi.org/10.3892/ijo.2014.2610
Copy and paste a formatted citation
x
Spandidos Publications style
Chen Y, Li J, Hu J, Zheng J, Zheng Z, Liu T, Lin Z and Lin M: Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells. Int J Oncol 45: 2076-2084, 2014.
APA
Chen, Y., Li, J., Hu, J., Zheng, J., Zheng, Z., Liu, T. ... Lin, M. (2014). Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells. International Journal of Oncology, 45, 2076-2084. https://doi.org/10.3892/ijo.2014.2610
MLA
Chen, Y., Li, J., Hu, J., Zheng, J., Zheng, Z., Liu, T., Lin, Z., Lin, M."Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells". International Journal of Oncology 45.5 (2014): 2076-2084.
Chicago
Chen, Y., Li, J., Hu, J., Zheng, J., Zheng, Z., Liu, T., Lin, Z., Lin, M."Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells". International Journal of Oncology 45, no. 5 (2014): 2076-2084. https://doi.org/10.3892/ijo.2014.2610
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