Radical Scavenging and Antiproliferative Effects of Cordycepin-Rich Ethanol Extract from Brown Rice-Cultivated Cordyceps militaris (Ascomycetes) Mycelium on Breast Cancer Cell Lines

Int J Med Mushrooms. 2019;21(7):657-669. doi: 10.1615/IntJMedMushrooms.2019031138.


The yield and efficacy of bioactive compounds from Cordyceps militaris fruiting bodies and its fermented grains usually vary with the strain used. In this study, we compared the antiproliferative, apoptotic, and antioxidative properties of ethanolic extracts of fruiting bodies and solid-stated fermented rice (FRE) from two wild-type strains of C. militaris applied to human breast cancer cell lines. We observed that FRE of the Zhangzhou strain (FRE-Z) produced a high level of cordycepin and exhibited comprehensive in vitro antioxidant activity against the oxidation of 2,2-diphenyl-1-picrylhydrazyl, superoxide, and hydroxyl radicals and low-density lipoprotein. Only FRE-Z exhibited dose-dependent inhibition of cell proliferation in MCF-7 (0.7 mg/mL) and MDA-MB-231 cells (1 mg/mL) after culturing for 24 h. The antiproliferative effects of FRE-Z were associated with an early stage of apoptosis induction at 4 h of treatment with 0.5 mg/mL FRE-Z in MCF-7 cells. The antiproliferative effect was determined to occur through p53 activation but not through the release of mitochondrial apoptosis-inducing factor or caspase-9 activation for an initial culture period of 16 h. In addition to a transient increase in cellular antioxidant enzyme, Cu/Zn superoxide dismutase was identified in MCF-7 cells after 2 h of treatment with FRE-Z. Therefore, FRE-Z, which exhibits various dose- and exposure time-dependent activities, has potential application in breast cancer chemoprevention.

MeSH terms

  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Cell Proliferation / drug effects*
  • Complex Mixtures / chemistry
  • Complex Mixtures / pharmacology*
  • Cordyceps / chemistry*
  • Ethanol
  • Female
  • Fermentation
  • Fruiting Bodies, Fungal / chemistry*
  • Humans
  • Hydroxyl Radical / metabolism
  • MCF-7 Cells
  • Mycelium / chemistry*
  • Oryza
  • Superoxide Dismutase / metabolism


  • Complex Mixtures
  • Hydroxyl Radical
  • Ethanol
  • Superoxide Dismutase