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

Xu-An Wang; Shan-Shan Xiang; Huai-Feng Li; Xiang-Song Wu; Mao-Lan Li; Yi-Jun Shu; Fei Zhang; Yang Cao; Yuan-Yuan Ye; Run-Fa Bao; Hao Weng; Wen-Guang Wu; Jia-Sheng Mu; Yun-Ping Hu; Lin Jiang; Zhu-Jun Tan; Wei Lu; Ping Wang; Ying-Bin Liu

doi:10.3390/molecules190811350

Molecules (Jul 2014)

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

Xu-An Wang,
Shan-Shan Xiang,
Huai-Feng Li,
Xiang-Song Wu,
Mao-Lan Li,
Yi-Jun Shu,
Fei Zhang,
Yang Cao,
Yuan-Yuan Ye,
Run-Fa Bao,
Hao Weng,
Wen-Guang Wu,
Jia-Sheng Mu,
Yun-Ping Hu,
Lin Jiang,
Zhu-Jun Tan,
Wei Lu,
Ping Wang,
Ying-Bin Liu

Affiliations

Xu-An Wang: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Shan-Shan Xiang: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Huai-Feng Li: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Xiang-Song Wu: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Mao-Lan Li: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yi-Jun Shu: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Fei Zhang: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yang Cao: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yuan-Yuan Ye: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Run-Fa Bao: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Hao Weng: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Wen-Guang Wu: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Jia-Sheng Mu: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Yun-Ping Hu: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Lin Jiang: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Zhu-Jun Tan: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Wei Lu: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
Ping Wang: Department of General Surgery, Hangzhou People's First Hospital, No. 261 Huansha Road, Hangzhou 310009, China
Ying-Bin Liu: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China

DOI: https://doi.org/10.3390/molecules190811350
Journal volume & issue: Vol. 19, no. 8
pp. 11350 – 11365

Abstract

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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.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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