Open Access

Bufadienolides induce p53-mediated apoptosis in esophageal squamous cell carcinoma cells in vitro and in vivo

  • Authors:
    • Shaohuan Lin
    • Junhong Lv
    • Panli Peng
    • Changqing Cai
    • Jianming Deng
    • Haihong Deng
    • Xuejun Li
    • Xinyue Tang
  • View Affiliations

  • Published online on: November 21, 2017     https://doi.org/10.3892/ol.2017.7457
  • Pages:1566-1572
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bufadienolides are a type of cardiotonic steroids isolated from the skin and parotid venom glands of the toad Bufo bufo gargarizans Cantor, and exhibit wide‑spectrum anticancer activities. However, the effects and mechanisms of bufadienolides on esophageal squamous cell carcinoma (ESCC) cells remain unknown. In the present study, the anticancer activities of two bufadienolides, bufotalin and bufalin, were examined in vitro and in vivo. The results demonstrated that bufotalin and bufalin effectively inhibited the viability of ESCC cells, with half‑maximal inhibitory concentration (IC50) values of 0.8‑3.6 µM. However, bufotalin and bufalin exhibited lower toxicity towards Het‑1A human esophageal squamous cells, indicating their high selectivity towards cancer cells. Mechanistic studies revealed that bufotalin effectively induced ESCC cell apoptosis, as characterized by DNA fragmentation and nuclear condensation, which was primarily mediated through activation of caspase family members. In addition, treatment of ESCC cells with bufotalin markedly activated tumor protein p53 (p53) phosphorylation. Transfection of cells with p53 small interfering RNA markedly inhibited bufotalin‑induced p53 phosphorylation and significantly inhibited bufotalin‑induced cell apoptosis. Furthermore, bufotalin demonstrated in vivo anticancer efficacy in a tumor‑bearing nude mice model, where bufotalin effectively inhibited Eca‑109 xenograft tumor growth in a time‑ and dose‑dependent manner, through activation of the p53 signaling pathway. Collectively, the results from the present study suggested that bufadienolides exert anticancer effects against ESCC by regulating the p53 signaling pathway.

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February 2018
Volume 15 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Lin, S., Lv, J., Peng, P., Cai, C., Deng, J., Deng, H. ... Tang, X. (2018). Bufadienolides induce p53-mediated apoptosis in esophageal squamous cell carcinoma cells in vitro and in vivo. Oncology Letters, 15, 1566-1572. https://doi.org/10.3892/ol.2017.7457
MLA
Lin, S., Lv, J., Peng, P., Cai, C., Deng, J., Deng, H., Li, X., Tang, X."Bufadienolides induce p53-mediated apoptosis in esophageal squamous cell carcinoma cells in vitro and in vivo". Oncology Letters 15.2 (2018): 1566-1572.
Chicago
Lin, S., Lv, J., Peng, P., Cai, C., Deng, J., Deng, H., Li, X., Tang, X."Bufadienolides induce p53-mediated apoptosis in esophageal squamous cell carcinoma cells in vitro and in vivo". Oncology Letters 15, no. 2 (2018): 1566-1572. https://doi.org/10.3892/ol.2017.7457