title: Cordycepin induces S phase arrest and apoptosis in human gallbladder cancer cells.
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.
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Xu-An
authors.initials: XA
authors.lastname: Wang
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Xiang
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Huai-Feng
authors.initials: HF
authors.lastname: Li
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Xiang-Song
authors.initials: XS
authors.lastname: Wu
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Mao-Lan
authors.initials: ML
authors.lastname: Li
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Shu
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ye
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Run-Fa
authors.initials: RF
authors.lastname: Bao
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Weng
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Wu
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Mu
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Hu
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Zhu-Jun
authors.initials: ZJ
authors.lastname: Tan
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Hangzhou People's First Hospital, No.261 Huansha Road, Hangzhou 310009, China. wangpinghz@tom.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China. liuybphd@126.com.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003839:Deoxyadenosines / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D047368:Tumor Burden / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D003839:Deoxyadenosines; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; C058120:cordycepin
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