Cordycepin inhibits migration of human glioblastoma cells by affecting lysosomal degradation and protein phosphatase activation

J Nutr Biochem. 2017 Mar;41:109-116. doi: 10.1016/j.jnutbio.2016.12.008. Epub 2016 Dec 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonium Chloride / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Deoxyadenosines / antagonists & inhibitors
  • Deoxyadenosines / pharmacology
  • Deoxyadenosines / therapeutic use*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Lysosomes / drug effects*
  • Lysosomes / metabolism
  • Lysosomes / pathology
  • Mice, Nude
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Okadaic Acid / pharmacology
  • Oxazoles / pharmacology
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / metabolism*
  • Proteolysis / drug effects
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Deoxyadenosines
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Oxazoles
  • Ammonium Chloride
  • Okadaic Acid
  • calyculin A
  • Phosphoprotein Phosphatases
  • cordycepin