期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 122, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2019.109763
关键词
Cinobufagin; Nasopharyngeal carcinoma; HK-1 cells; Mitochondria-mediated apoptosis; Cell cycle arrest
资金
- National Natural Science Foundation of China [81872162, 81602556, 31870338]
- Shandong Provincial Natural Science Foundation, China [ZR2017JL030]
- Key Research and Development Program of Shandong Province of China [2019GSF108214]
- Taishan Scholars Construction Engineering of Shandong Province
- Yantai High-End Talent Introduction Plan Double Hundred
- Dominant Disciplines' Talent Team Development Scheme of Higher Education of Shandong Province
Emerging evidence suggests that cinobufagin, an active ingredient in Venenum Bufonis, inhibits cell proliferation in several tumor cells. However, the anti-tumor effect of cinobufagin on nasopharyngeal carcinoma and the underlying molecular mechanisms are still unclear. In this study, we found that cinobufagin significantly inhibits the proliferation of nasopharyngeal carcinoma HK-1 cells. Further analyses demonstrated that cinobufagin induces cell cycle arrest at the S phase in HK-1 cells through downregulating the levels of CDK2 and cyclin E. Moreover, cinobufagin significantly downregulates the protein level of Bcl-2 and upregulates the levels of Bax, subsequently increasing the levels of cytoplasmic cytochrome c, Apaf-1, cleaved PARP1, cleaved caspase-3, and cleaved caspase-9, leading to HK-1 apoptosis. Furthermore, we found that cinobufagin significantly increases ROS levels and decreases the mitochondrial membrane potential in HK-1 cells. Collectively, these data imply that cinobufagin induces cell cycle arrest at the S phase and induces apoptosis through increasing ROS levels, thereby inhibiting cell proliferation in HK-1 cells. Therefore, cinobufagin is a promising bioactive agent that may contribute to the development of treatment strategies of nasopharyngeal carcinoma.
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