イソチオシアネートによるがん予防の可能性 : 細胞増殖の選択的制御とその分子機構(第15回公開シンポジウム「食べ物によるがん予防戦略を考える : 生活環境中の植物成分の抗変異・抗発がん作用とそのメカニズム」)

概要

論文の詳細を見る
An important group of compounds that have a chemopreventive property is organosulfur compounds such as isothiocyanates. In the present study, we clarified the molecular mechanism underlying the relationship between benzyl isothiocyanate (BITC)-induced cell cycle arrest and apoptosis. The exposure of the cultured cells to BITC resulted in the inhibition of the G_2/M progression that coincided with apoptosis induction. An experiment using phase-specific synchronized cells demonstrated that the G_2/M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We identified phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with JNK activation by BITC. We also found that BITC induced a cytotoxic effect more preferentially in the proliferating normal human colon epithelial cells than the quiescent cells. Moreover, down-regulation of p53 resulted in the enhancement of susceptibility to undergoing apoptotic stimulation by BITC. These findings suggested that p53 might play a negative regulating role in BITC-induced apoptosis. In conclusion, the results from this study provided biological evidence that BITC has a potential to induce apoptosis selectively in p53-mutated proliferating pre-cancerous cells.
日本環境変異原学会の論文
2004-12-20