Hydrogen sulfide protects H9c2 cardiac cells against doxorubicin-induced cytotoxicity through the PI3K/Akt/FoxO3a pathway

  • Authors:
    • Mi-Hua Liu
    • Yuan Zhang
    • Jun He
    • Tian-Ping Tan
    • Shao-Jian Wu
    • Dong-Ming Guo
    • Hui He
    • Juan Peng
    • Zhi-Han Tang
    • Zhi-Sheng Jiang
  • View Affiliations

  • Published online on: April 14, 2016     https://doi.org/10.3892/ijmm.2016.2563
  • Pages: 1661-1668
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Abstract

Doxorubicin (DOX) is an efficient drug used in cancer therapy that also produces reactive oxygen species (ROS) that induces severe cytotoxicity, which limits its clinical application. Hydrogen sulfide (H2S), a novel gasotransmitter, has been shown to exert cardioprotective effects. The present study aimed to determine whether exogenous H2S protects H9c2 cardiac cells against DOX-induced cytotoxicity and whether these protective effects are mediated through the PI3K/Akt/FoxO3a pathway. The H9c2 cardiac cells were exposed to 5 µM DOX for 24 h to establish a model of DOX-induced cardiotoxicity. The results showed that the treatment of H9c2 cardiac cells with sodium hydrosulfide (NaHS) for 30 min prior to DOX exposure markedly attenuated the phosphorylation of Akt and FoxO3a. Notably, pre-treatment of the H9c2 cells with NaHS significantly attenuated the nuclear localization of FoxO3a as well as the apoptosis of H9c2 cells induced by DOX. The treatment of H9c2 cells with N-acetyl-L-cysteine (NAC), a scavenger of ROS, prior to DOX exposure, also markedly increased the phosphorylation of Akt and FoxO3a which was inhibited by DOX alone. Furthermore, pre-treatment with LY294002, a selective inhibitor of PI3K/Akt, reversed the protective effect of H2S against DOX-induced injury of cardiomyocytes, as demonstrated by an increased number of apoptotic cells, a decrease in cell viability and the reduced phosphorylation of Akt and FoxO3a. These findings suggested that exogenous H2S attenuates DOX-induced cytotoxic effects in H9c2 cardiac cells through the PI3K/Akt/FoxO3a pathway.
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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 M, Zhang Y, He J, Tan T, Wu S, Guo D, He H, Peng J, Tang Z, Jiang Z, Jiang Z, et al: Hydrogen sulfide protects H9c2 cardiac cells against doxorubicin-induced cytotoxicity through the PI3K/Akt/FoxO3a pathway. Int J Mol Med 37: 1661-1668, 2016
APA
Liu, M., Zhang, Y., He, J., Tan, T., Wu, S., Guo, D. ... Jiang, Z. (2016). Hydrogen sulfide protects H9c2 cardiac cells against doxorubicin-induced cytotoxicity through the PI3K/Akt/FoxO3a pathway. International Journal of Molecular Medicine, 37, 1661-1668. https://doi.org/10.3892/ijmm.2016.2563
MLA
Liu, M., Zhang, Y., He, J., Tan, T., Wu, S., Guo, D., He, H., Peng, J., Tang, Z., Jiang, Z."Hydrogen sulfide protects H9c2 cardiac cells against doxorubicin-induced cytotoxicity through the PI3K/Akt/FoxO3a pathway". International Journal of Molecular Medicine 37.6 (2016): 1661-1668.
Chicago
Liu, M., Zhang, Y., He, J., Tan, T., Wu, S., Guo, D., He, H., Peng, J., Tang, Z., Jiang, Z."Hydrogen sulfide protects H9c2 cardiac cells against doxorubicin-induced cytotoxicity through the PI3K/Akt/FoxO3a pathway". International Journal of Molecular Medicine 37, no. 6 (2016): 1661-1668. https://doi.org/10.3892/ijmm.2016.2563