Open Access

Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo

  • Authors:
    • Yu‑Jui Kuo
    • Yan‑Jin Liu
    • Tzong‑Der Way
    • Su‑Yin Chiang
    • Jaung‑Geng Lin
    • Jing‑Gung Chung
  • View Affiliations

  • Published online on: April 27, 2017     https://doi.org/10.3892/etm.2017.4392
  • Pages: 3388-3396
  • Copyright: © Kuo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Arsenic trioxide (ATO) is clinically used to treat acute promyelocytic leukemia (APL); however, the therapeutic dose of ATO may prompt critical cardiac side effects. Combination therapy may be used to improve the therapeutic efficiency. To evaluate this possibility, the present study determined the combined effects of Hedyotis diffusa Willd (HDW) extract and ATO in leukemic WEHI‑3 cells. The results demonstrated that co‑treatment of HDW with ATO resulted in a synergistic augmentation of cytotoxicity in cells at the concentration tested. In order to investigate the potential therapeutic application for leukemia, the combined effects of HDW and ATO were analyzed on the WEHI‑3 cell‑induced orthotopic leukemia animal model in vivo. The WEHI‑3 cells in mice with leukemia were established by injecting murine WEHI‑3 cells into BALB/c mice, and treating them with HDW and/or combined with ATO. The results indicated that HDW alone or HDW combined with ATO promoted the total survival rate of mice with leukemia, and these effects are dose‑dependent. HDW alone or HDW combined with ATO did not affect the body weight, decreased the spleen weight and did not affect the liver weight. Furthermore, the results demonstrated that HDW alone or HDW combined with ATO resulted in a synergistic augmentation of apoptosis in WEHI‑3 cells at the concentration tested. In order to further reveal the detailed mechanism of this synergistic effect on apoptosis, apoptosis‑related proteins were also evaluated. The data revealed that HDW alone or HDW combined with ATO induced the expression of death receptor 4 (DR4) and DR5 and the activation of poly adenosine diphosphate ribose polymerase, caspase‑3, ‑8 and ‑9. Furthermore, HDW alone or HDW combined with ATO decreased the expression levels of B‑cell lymphoma 2, B‑cell lymphoma‑extra large and survivin, and increased the expression levels of Bak and t‑Bid. Altogether, the results indicate that the combination of HDW with ATO may be a promising strategy used to increase the clinical efficacy of ATO in the treatment of APL.

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June-2017
Volume 13 Issue 6

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Spandidos Publications style
Kuo YJ, Liu YJ, Way TD, Chiang SY, Lin JG and Chung JG: Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo. Exp Ther Med 13: 3388-3396, 2017
APA
Kuo, Y., Liu, Y., Way, T., Chiang, S., Lin, J., & Chung, J. (2017). Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo. Experimental and Therapeutic Medicine, 13, 3388-3396. https://doi.org/10.3892/etm.2017.4392
MLA
Kuo, Y., Liu, Y., Way, T., Chiang, S., Lin, J., Chung, J."Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo". Experimental and Therapeutic Medicine 13.6 (2017): 3388-3396.
Chicago
Kuo, Y., Liu, Y., Way, T., Chiang, S., Lin, J., Chung, J."Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo". Experimental and Therapeutic Medicine 13, no. 6 (2017): 3388-3396. https://doi.org/10.3892/etm.2017.4392