Cordycepin Induces S Phase Arrest and Apoptosis in Human Gallbladder Cancer Cells

Molecules

Xu-An Wang¹  Shan-Shan Xiang¹  Huai-Feng Li¹  Xiang-Song Wu¹  Mao-Lan Li¹  Yi-Jun Shu¹  Fei Zhang¹  Yang Cao¹  Yuan-Yuan Ye¹  Run-Fa Bao¹  Hao Weng¹  Wen-Guang Wu¹  Jia-Sheng Mu¹  Yun-Ping Hu¹  Lin Jiang¹  Zhu-Jun Tan¹  Wei Lu¹  Ping Wang² 

[1]Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China

[2]Department of General Surgery, Hangzhou People’s First Hospital, No. 261 Huansha Road, Hangzhou 310009, China

关键词: cordycepin;    gallbladder cancer cells;    proliferation;    cell cycle;    apoptosis;   

DOI  :  10.3390/molecules190811350

来源: mdpi

【 摘 要 】

Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells). Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI) double-staining assay, and the mitochondrial membrane potential (ΔΨm) decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.