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Molecules 2014, 19(8), 11350-11365; doi:10.3390/molecules190811350

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

1,2,3,†, 1,2,3,†, 1,2,3,†, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 1,2,3, 4,* and 1,2,3,*
1
Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
2
Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
3
Department of General Surgery, School of Medicine, Shanghai Jiao Tong University, No. 1665 Kongjiang Road, Shanghai 200092, China
4
Department of General Surgery, Hangzhou People's First Hospital, No. 261 Huansha Road, Hangzhou 310009, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 20 June 2014 / Revised: 21 July 2014 / Accepted: 22 July 2014 / Published: 31 July 2014
(This article belongs to the Section Natural Products)
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Abstract

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. View Full-Text
Keywords: cordycepin; gallbladder cancer cells; proliferation; cell cycle; apoptosis cordycepin; gallbladder cancer cells; proliferation; cell cycle; apoptosis
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Wang, X.-A.; Xiang, S.-S.; Li, H.-F.; Wu, X.-S.; Li, M.-L.; Shu, Y.-J.; Zhang, F.; Cao, Y.; Ye, Y.-Y.; Bao, R.-F.; Weng, H.; Wu, W.-G.; Mu, J.-S.; Hu, Y.-P.; Jiang, L.; Tan, Z.-J.; Lu, W.; Wang, P.; Liu, Y.-B. Cordycepin Induces S Phase Arrest and Apoptosis in Human Gallbladder Cancer Cells. Molecules 2014, 19, 11350-11365.

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