title: Naturally occurring phenethyl isothiocyanate-induced inhibition of gastric cancer cell growth by disruption of microtubules.
abstract: OBJECTIVE
  Phenethyl isothiocyanate (PEITC) derives from vegetables commonly consumed by man and has been demonstrated as a promising chemopreventive agent against several types of cancer. However, the potential in preventing gastric cancer as well as the underlying mechanisms are to date not fully understood. The present study aimed at elucidating the cellular effects induced by PEITC in gastric cancer cells leading to apoptosis.
  
  
  METHODS
  The human gastric cancer cell lines Kato-III and MKN74 were employed. Cell proliferation was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Morphology and migration were investigated through a contrast microscope. Cell cycle distribution was analyzed using flow cytometry of PI-stained cells. Microtubules were studied by confocal detection of Kato-III cells transfected to express GFP-tagged microtubules. Commercial kits were employed to study the effect of PEITC on apoptosis, caspase-3 activity, and glutathione content in MKN74 cells.
  
  
  RESULTS
  Kato-III and MKN74 cells responded, with different sensitivity, dose- and time-dependently in inhibition of cell proliferation to PEITC treatment. Further, PEITC induced aberrated cell morphologies and inhibited migration of MKN74 cells. Kato-III cells treated with PEITC accumulated in G2 /M phase and displayed a loss of microtubuli with the subsequent formation of apoptotic bodies. Although weak responses, MKN74 cells also accumulated in G2 /M phase, became apoptotic, increased caspase-3 activity, and suffered a reduction of glutathione pool.
  
  
  CONCLUSIONS
  Our findings demonstrate that PEITC induces disintegration of microtubules in human gastric cancer cells contributing to cell cycle arrest and ultimately apoptosis, contributing to an increased understanding of PEITC-induced inhibition of gastric cancer cell growth.
authors.affiliation: Department of Biology, The Norwegian University of Science and Technology, Trondheim, Norway; Department of Cancer Research and Molecular Medicine, The Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Øverby
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Zhao
authors.forename: Atle Magnar
authors.initials: AM
authors.lastname: Bones
authors.forename: Duan
authors.initials: D
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D008870:Microtubules / Q000187:drug effects* / Q000473:pathology*; D008517:Phytotherapy; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control / Q000648:ultrastructure*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017879:Isothiocyanates; C058305:phenethyl isothiocyanate; D053148:Caspase 3; D005978:Glutathione
keywords: apoptosis; gastric cancer; isothiocyanates; microtubules