Arenobufagin induces cell apoptosis by modulating the cell cycle regulator claspin and the JNK pathway in nasopharyngeal carcinoma cells.

Abstract

BACKGROUND The high recurrence rate and incidence of distant metastasis of nasopharyngeal carcinoma (NPC) result in poor prognosis. Natural compounds that can complement combination radiation therapy need to be identified. Arenobufagin is commonly used for heart diseases and liver cancer, but its effectiveness in NPC is unclear. STUDY DESIGN AND METHODS The effect of arenobufagin-induced apoptosis was measured by a cell viability assay, tumorigenic assay, fluorescence assay, and Western blot assay through NPC-039 and NPC-BM cell lines. The protease array, Western blot assay, and transient transfection were used to investigate the underlying mechanism of arenobufagin-induced apoptosis. A NPC xenograft model was established to explore the antitumor activity of arenobufagin in vivo. RESULTS Our findings indicated that arenobufagin exerted cytotoxic effects on NPC cells, inhibiting proliferation through apoptosis activation. The downregulation of claspin was confirmed in arenobufagin-induced apoptosis. The combined treatment of arenobufagin and inhibitors of mitogen-activated protein kinase demonstrated that arenobufagin induced NPC apoptosis through the c-Jun N-terminal kinases (JNK) pathway inhibition. Furthermore, arenobufagin suppressed NPC tumor proliferation in vivo. CONCLUSION Our results revealed the antitumor effect of arenobufagin in vitro and in vivo. Arenobufagin may provide clinical utility on NPC due to the suppression of claspin and the JNK pathway.