The induction of apoptosis and autophagy by Wasabia japonica extract in colon cancer

Eur J Nutr. 2016 Mar;55(2):491-503. doi: 10.1007/s00394-015-0866-5. Epub 2015 Feb 27.

Abstract

Purpose: Wasabia japonica (wasabi) has been shown to exhibit properties of detoxification, anti-inflammation and the induction of apoptosis in cancer cells. This study aimed to investigate the molecular mechanism of the cytotoxicity of wasabi extract (WE) in colon cancer cells to evaluate the potential of wasabi as a functional food for chemoprevention.

Methods: Colo 205 cells were treated with different doses of WE, and the cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Apoptosis and autophagy were detected by 4',6-diamidino-2-phenylindole, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbo-yanine iodide and staining for acidic vascular organelles (AVOs), along with Western blotting.

Results: The results demonstrated that WE induced the extrinsic pathway and mitochondrial death machinery through the activation of TNF-α, Fas-L, caspases, truncated Bid and cytochrome C. WE also induced autophagy by decreasing the phosphorylation of Akt and mTOR and promoting the expression of microtubule-associated protein 1 light chain 3-II and AVO formation. An in vivo xenograft model verified that tumor growth was delayed by WE treatment.

Conclusion: Our studies revealed that WE exhibits anti-colon cancer properties through the induction of apoptosis and autophagy. These results provide support for the application of WE as a chemopreventive functional food and as a prospective treatment of colon cancer.

Keywords: Apoptosis; Autophagy; Colon cancer; RAD001; Wasabia japonica.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • BH3 Interacting Domain Death Agonist Protein / genetics
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Cell Line, Tumor / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Cytochromes c / genetics
  • Cytochromes c / metabolism
  • Humans
  • Indoles / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tetrazolium Salts / metabolism
  • Thiazoles / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Wasabia / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • BH3 Interacting Domain Death Agonist Protein
  • Indoles
  • Microtubule-Associated Proteins
  • Plant Extracts
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • DAPI
  • Cytochromes c
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • thiazolyl blue