Article Publish Status: FREE
Abstract Title:

Bufadienolides induce p53-mediated apoptosis in esophageal squamous cell carcinoma cellsand.

Abstract Source:

Oncol Lett. 2018 Feb ;15(2):1566-1572. Epub 2017 Nov 21. PMID: 29434851

Abstract Author(s):

Shaohuan Lin, Junhong Lv, Panli Peng, Changqing Cai, Jianming Deng, Haihong Deng, Xuejun Li, Xinyue Tang

Article Affiliation:

Shaohuan Lin


Bufadienolides are a type of cardiotonic steroids isolated from the skin and parotid venom glands of the toadCantor, 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 examinedand. The results demonstrated that bufotalin and bufalin effectively inhibited the viability of ESCC cells, with half-maximal inhibitory concentration (IC) values of 0.8-3.6µM. 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 nuclearcondensation, 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 demonstratedanticancer 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.

Study Type : Animal Study, In Vitro Study

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