Valproic acid enhances the antileukemic effect of cytarabine by triggering cell apoptosis

  • Authors:
    • Nan Liu
    • Chen Wang
    • Libing Wang
    • Lei Gao
    • Hui Cheng
    • Gusheng Tang
    • Xiaoxia Hu
    • Jianmin Wang
  • View Affiliations

  • Published online on: April 8, 2016     https://doi.org/10.3892/ijmm.2016.2552
  • Pages: 1686-1696
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Abstract

Acute myeloid leukemia (AML) is an aggressive clonal malignancy of hematopoietic progenitor cells with a poor clinical outcome. The resistance of leukemia cells to contemporary chemotherapy is one of the most formidable obstacles to treating AML. Combining valproic acid (VPA) with other anti-leukemic agents has previously been noted as a useful and necessary strategy which can be used to specifically induce anticancer gene expression. In the present study, we demonstrated the synergistic antileukemic activities between VPA and cytarabine (Ara‑C) in a retrovirus-mediated murine model with MLL-AF9 leukemia, three leukemia cell lines (THP-1, K562 and HL-60) and seven primary human AML samples. Using RT-qPCR, we noted that the combination of VPA and Ara‑C significantly upregulated Bax expression and led to the arrest of leukemia cell proliferation, sub-G1 DNA accumulation and cell apoptosis, as demonstrated by flow cytometric analysis. Significantly, further experiments revealed that knockdown of Bax expression prevented VPA and Ara‑C‑induced cell apoptosis in THP-1 cells. The results of our present study demonstrated the synergistic antileukemic effect of combined VPA and Ara‑C treatment in AML, and thus we suggest that VPA be used an alternative treatment for AML.
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June-2016
Volume 37 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Liu N, Wang C, Wang L, Gao L, Cheng H, Tang G, Hu X and Wang J: Valproic acid enhances the antileukemic effect of cytarabine by triggering cell apoptosis. Int J Mol Med 37: 1686-1696, 2016.
APA
Liu, N., Wang, C., Wang, L., Gao, L., Cheng, H., Tang, G. ... Wang, J. (2016). Valproic acid enhances the antileukemic effect of cytarabine by triggering cell apoptosis. International Journal of Molecular Medicine, 37, 1686-1696. https://doi.org/10.3892/ijmm.2016.2552
MLA
Liu, N., Wang, C., Wang, L., Gao, L., Cheng, H., Tang, G., Hu, X., Wang, J."Valproic acid enhances the antileukemic effect of cytarabine by triggering cell apoptosis". International Journal of Molecular Medicine 37.6 (2016): 1686-1696.
Chicago
Liu, N., Wang, C., Wang, L., Gao, L., Cheng, H., Tang, G., Hu, X., Wang, J."Valproic acid enhances the antileukemic effect of cytarabine by triggering cell apoptosis". International Journal of Molecular Medicine 37, no. 6 (2016): 1686-1696. https://doi.org/10.3892/ijmm.2016.2552