Open Access

The anticancer effects of cinobufagin on hepatocellular carcinoma Huh‑7 cells are associated with activation of the p73 signaling pathway

  • Authors:
    • Lei Zhao
    • Lina Fu
    • Zhongwei Xu
    • Rong Fan
    • Ruicheng Xu
    • Rong Fu
    • Shuang Zou
    • Congcong Wang
    • Yan Zhang
    • Jiabao Wang
    • Jun Bao
    • Zhimei Wang
    • Xiaojie Hou
    • Yupiao Zheng
    • Erqing Dai
    • Fengmei Wang
  • View Affiliations

  • Published online on: March 29, 2019     https://doi.org/10.3892/mmr.2019.10108
  • Pages: 4119-4128
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Na+/K+‑ATPase inhibitor cinobufagin exhibits numerous anticancer effects on hepatocellular carcinoma (HCC) cells expressing wild‑type p53 via inhibition of aurora kinase A (AURKA) and activation of p53 signaling. However, the effects of cinobufagin on HCC cells expressing mutant p53 remain unclear. In the present study, the anticancer effects of cinobufagin were investigated on HCC Huh‑7 cells with mutant p53, and the effects of AURKA overexpression or inhibition on the anticancer effects of cinobufagin were analyzed. Viability, cell cycle progression and apoptosis of cells were determined using an MTT assay, flow cytometry and Hoechst 33342 staining, respectively. The expression levels of p53 and p73 signaling‑associated proteins were investigated via western blot analysis. The results demonstrated that the expression levels of AURKA, B‑cell lymphoma 2 (Bcl‑2), cyclin‑dependent kinase 1, cyclin B1, proliferating cell nuclear antigen and heterogeneous nuclear ribonucleoprotein K, as well as the phosphorylation of p53 and mouse double minute 2 homolog, were significantly decreased in Huh‑7 cells treated with 5 µmol/l cinobufagin for 24 h. Conversely, the expression levels of Bcl‑2‑associated X protein, p21, p53 upregulated modulator of apoptosis and phorbol‑12‑myristate‑13‑acetate‑induced protein 1, were significantly increased by cinobufagin treatment. Overexpression or inhibition of AURKA suppressed or promoted the anticancer effects of cinobufagin on Huh‑7 cells, respectively. These results indicated that cinobufagin may induce anticancer effects on Huh‑7 cells via the inhibition of AURKA and p53 signaling, and via the activation of p73 signaling, in an AURKA‑dependent manner.
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May-2019
Volume 19 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Zhao L, Fu L, Xu Z, Fan R, Xu R, Fu R, Zou S, Wang C, Zhang Y, Wang J, Wang J, et al: The anticancer effects of cinobufagin on hepatocellular carcinoma Huh‑7 cells are associated with activation of the p73 signaling pathway. Mol Med Rep 19: 4119-4128, 2019.
APA
Zhao, L., Fu, L., Xu, Z., Fan, R., Xu, R., Fu, R. ... Wang, F. (2019). The anticancer effects of cinobufagin on hepatocellular carcinoma Huh‑7 cells are associated with activation of the p73 signaling pathway. Molecular Medicine Reports, 19, 4119-4128. https://doi.org/10.3892/mmr.2019.10108
MLA
Zhao, L., Fu, L., Xu, Z., Fan, R., Xu, R., Fu, R., Zou, S., Wang, C., Zhang, Y., Wang, J., Bao, J., Wang, Z., Hou, X., Zheng, Y., Dai, E., Wang, F."The anticancer effects of cinobufagin on hepatocellular carcinoma Huh‑7 cells are associated with activation of the p73 signaling pathway". Molecular Medicine Reports 19.5 (2019): 4119-4128.
Chicago
Zhao, L., Fu, L., Xu, Z., Fan, R., Xu, R., Fu, R., Zou, S., Wang, C., Zhang, Y., Wang, J., Bao, J., Wang, Z., Hou, X., Zheng, Y., Dai, E., Wang, F."The anticancer effects of cinobufagin on hepatocellular carcinoma Huh‑7 cells are associated with activation of the p73 signaling pathway". Molecular Medicine Reports 19, no. 5 (2019): 4119-4128. https://doi.org/10.3892/mmr.2019.10108