Previous studies with ITCs and stomach cancer have shown an inverted correlation between intake of ITC-rich diet and risk of cancer.[7] Furthermore, the broccoli-derived http://www.selleckchem.com/screening/kinase-inhibitor-library.html SFN was reported to eradicate

the gastric cancer-related bacterium H. pylori from a gastric cancer cell line and presumably reduced the cell count of these bacteria in the stomach of human patients.[18, 23] Prevention of chemically induced gastric cancer in mice by SFN was linked to the nrf2 gene as nrf2 knockout mice did not respond equally strong in cancer prevention to an SFN-rich diet.[18] To the best our knowledge, no in vivo experiments on gastric cancer with PEITC have been reported so far, which we in parallel to this study is currently undertaking. However, in in vitro studies, PEITC has been shown to attenuate cell Selleckchem CH5424802 migration and invasion of human gastric cancer AGS cell line.[17] Suppression of MAPK and NFκB signaling pathways were pointed

out as key underlying factors. Similar findings were made when another aromatic ITC, benzyl ITC, was applied to AGS cells.[24] Although our findings are the first to show the loss of microtubular filaments in gastric cancer cells treated with PEITC, in lung cancer cells, Mi and colleagues identified α- and β-tubulins, monomers of microtubuli as binding targets for PEITC.[12] Moreover, in bladder cancer cells, binding of the aliphatic allyl ITC to α- and β-tubulins led to subsequent ubiquitination and degradation of tubulins as well as onset of a mitotic cell cycle arrest and ultimately apoptosis.[21] In prostate cancer cells, PEITC was shown to induce G2/M cell cycle MYO10 arrest as well as downregulation of gene expression of α- and β-tubulins.[25] In breast cancer cells, SFN was shown to suppress the dynamic instability of microtubules leading to mitotic arrest of these cells.[26] Taken together, we suggest that PEITC binds to α- and β-tubulins with the subsequent

degradation of these monomers leading to a deformation of microtubular filaments which in turn contributes to accumulation of cells in G2/M phase and apoptosis in gastric cancer cell line Kato-III. Upon entering a cell, PEITC inevitably binds to the abundantly present redox mediator GSH. Binding and conjugation with GSH leads to a decrease in the intracellular GSH pool and secondary effects including generation of ROS. It has been suggested that this mechanism is essential in the selective toxicity of PEITC in cancerous cells compared with their normal equivalents.[27] Cell line MKN74 tested in the present study displayed a lower sensitivity to PEITC when proliferation was assayed. Furthermore, these cells showed a weak response in GSH reduction, increase of apoptotic cells, and increase in caspase-3 activity. When testing higher concentrations than those presented here, we observed high amount of cell death and could not obtain reproducible data.