title: Cordycepin inhibits migration of human glioblastoma cells by affecting lysosomal degradation and protein phosphatase activation.
abstract: Cordycepin, a nucleoside-derivative-isolated form Cordyceps militaris, has been reported to suppress tumor cell proliferation and cause apoptosis. This study investigates the effect of cordycepin on the migration of human glioblastoma cells. Cordycepin suppressed the migration of the human glioblastoma cell lines U87MG and LN229 in transwell and wound healing assays. Cordycepin decreased protein expression of integrin α1, focal adhesion kinase (FAK), p-FAK, paxillin and p-paxillin. The lysosomal inhibitor NH4Cl blocked the ability of cordycepin to inhibit focal adhesion protein expression and glioma cell migration. In addition, the protein phosphatase inhibitors calyculin A and okadaic acid blocked the cordycepin-mediated reduction in p-Akt, p-FAK and migration. Hematoxylin and eosin staining of mouse xenografts demonstrated that cordycepin reduced brain tumor size in vivo. In conclusion, cordycepin inhibited migration of human glioblastoma cells by affecting lysosomal degradation and protein phosphatase activation. This pathway may be a useful target for clinical therapy in the future.
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Penghu Branch of Tri-Service General Hospital, Magong, Penghu, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Dueng-Yuan
authors.initials: DY
authors.lastname: Hueng
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wen-Chiuan
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: ychen0523@mail.ndmctsgh.edu.tw.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003839:Deoxyadenosines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008387:Marine Toxins; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D009363:Neoplasm Proteins; D010080:Oxazoles; D000643:Ammonium Chloride; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; C058120:cordycepin