title: Cordycepin Affects Multiple Apoptotic Pathways to Mediate Hepatocellular Carcinoma Cell Death.
abstract: BACKGROUND
  Cordycepin possesses anti-inflammatory, anti-metastatic and anti-tumor properties.
  
  
  OBJECTIVE
  The present study investigates the anti-hepatocellular carcinoma activities of cordycepin in in vitro and in vivo models.
  
  
  METHODS
  Cell viability, apoptosis rate, intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were determined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide bromide assay, annexin V/propidium iodide double staining, 2',7'-dichlorfluorescein-diacetate and 5,5',6,6'-tetrachloro-1,1',3,3' tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining respectively. The expressions of pro-apoptosis and antiapoptosis proteins were detected by western blot. A PLC/PRL/5-xenografted nude mouse model was applied to further confirm the anti-tumor activities of cordycepin.
  
  
  RESULTS
  Cordycepin suppressed cell viability, enhanced apoptotic rate, inhibited cell proliferation and increased cleaved poly (ADP-ribose) polymerase (PARP) level. Apoptotic alteration on mitochondria and abnormal changes on b-cell lymphoma 2 (Bcl-2) and b-cell lymphoma-extra large (Bcl-xL) levels were observed in cordycepin-treated cells. Furthermore, cordycepin suppressed the activation of extracellular signaling-regulated kinase (ERKs) and mammalian target of rapamycin (mTOR) in both PLC/PRF/5 and HepG2 cells. Finally, PLC/PRL/5-xengrafted BALB/c athymic nude mice were performed to confirm cordycepin's anti-tumor action.
  
  
  CONCLUSIONS
  Our finding suggests that the anti-hepatocellular carcinoma properties of cordycepin are related to its modulation of multiple anti-apoptotic and pro-apoptotic pathways. Our study provides an experimental evidence for cordycepin as a rational agent for hepatocellular carcinoma treatment.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Guo
authors.forename: Qingfan
authors.initials: Q
authors.lastname: Meng
authors.forename: Jiahui
authors.initials: J
authors.lastname: Lu
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liang
authors.forename: Yutong
authors.initials: Y
authors.lastname: Quan
authors.affiliation: School of Life Sciences, Jilin University, Changchun City, Jilin Province, PR China. China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D017382:Reactive Oxygen Species; C058120:cordycepin