Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth

Sci Rep. 2020 Aug 25;10(1):14174. doi: 10.1038/s41598-020-71118-3.


Mitochondrial dysfunction and significant changes in metabolic pathways accompany cancer development and are responsible for maintaining the tumor microenvironment. Normal mitochondria can trigger intrinsic apoptosis by releasing cytochrome c into the cytosol. The survival of malignant cells highly depends on the suppression of this function. We validated that A250, a highly purified fraction of fermented wheat germ extract (FWGE), increases the carbon flux into the mitochondria, the expression of key elements of the Krebs cycle and oxidative phosphorylation (OXPHOS). The increased respiratory chain activity is related to the mitochondria's ability to release cytochrome c into the cytosol, which triggers the apoptotic cascade. The 68% tumor growth inhibitory effect observed in the murine melanoma study is related to this effect, as proteomic analysis validated similar changes in mitochondrial protein levels in the isolated tumor tissue samples. Blood count data indicated that this effect was not accompanied by general toxicity. This study is significant, as it shows that a highly concentrated form of FWGE is an effective agent that increases normal mitochondrial functionality. The lack of hepatotoxic and general toxic effects makes A250 an excellent candidate targeting mitochondria function in cancer therapy.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carbon / metabolism
  • Cell Line, Tumor
  • Citric Acid Cycle / drug effects
  • Cytochromes c / metabolism
  • Drug Screening Assays, Antitumor
  • Fermentation
  • Gene Expression Regulation, Neoplastic / drug effects
  • HEK293 Cells
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Melanoma, Experimental / drug therapy
  • Methanol
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Phosphorylation / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / toxicity
  • Random Allocation
  • Solvents
  • Triticum / chemistry*
  • Warburg Effect, Oncologic / drug effects*


  • Plant Extracts
  • Solvents
  • Carbon
  • Cytochromes c
  • Methanol