机构：[1]Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215001, China[2]Department of Burn Surgery, The Linyi People’s Hospital, Linyi 276000, China[3]Department of Radiotherapy, Hubei Cancer Hospital, Wuhan 430000, China[4]Department of Hand and Foot Surgery, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215001, China
Hepatocellular carcinoma (HCC) is a highly aggressive and lethal neoplasm with poor prognosis. The aim of this study is to investigate the anticancer activity of cinobufotalin, a bufadienolide isolated from toad venom, in cultured HCC cells, and to study the underlying mechanisms. We found that cinobufotalin (at nmol/L) significantly inhibited HCC cell growth and survival while inducing considerable cell apoptosis. Further, cinobufotalin inhibited sphingosine kinase 1 (SphK1) activity and induced pro-apoptotic ceramide production. Ceramide synthase-1 small hairpin RNA (shRNA)-depletion inhibited cinobufotalin-induced ceramide production and HCC cell apoptosis. On the other hand, the glucosylceramide synthase (GCS) inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) facilitated cinobufotalin-induced ceramide production and cell apoptosis. SphK1 inhibitor II (SKI-II), similar to cinobufotalin, increased cellular ceramide level and promoted HCC cell apoptosis. Finally, we observed that cinobufotalin inactivated Akt-S6K1 signaling in HepG2 cells, which was again inhibited by ceramide synthase-1 shRNA-depletion. In conclusion, the results of this study suggest that cinobufotalin induces growth inhibition and apoptosis in cultured HCC cells through ceramide production. Cinobufotalin may be investigated as a novel anti-HCC agent.
基金：
This work was supported by the National Natural
Science Foundation
第一作者机构：[1]Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215001, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215001, China
推荐引用方式(GB/T 7714)：
Long Cheng,Yuan-zheng Chen,Yi Peng,et al.Ceramide production mediates cinobufotalin-induced growth inhibition and apoptosis in cultured hepatocellular carcinoma cells[J].TUMOR BIOLOGY.2015,36(8):5763-71.doi:10.1007/s13277-015-3245-1.
APA：
Long Cheng,Yuan-zheng Chen,Yi Peng,Nan Yi,Xin-shi Gu...&Xu-ming Bai.(2015).Ceramide production mediates cinobufotalin-induced growth inhibition and apoptosis in cultured hepatocellular carcinoma cells.TUMOR BIOLOGY,36,(8)
MLA：
Long Cheng,et al."Ceramide production mediates cinobufotalin-induced growth inhibition and apoptosis in cultured hepatocellular carcinoma cells".TUMOR BIOLOGY 36..8(2015):5763-71
