環境変異原研究
Online ISSN : 1880-7054
Print ISSN : 0910-0865
ISSN-L : 0910-0865
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-」
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—
中村 宜督
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ジャーナル フリー

2004 年 26 巻 3 号 p. 253-258

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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 G2/M progression that coincided with apoptosis induction. An experiment using phase-specific synchronized cells demonstrated that the G2/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.

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© 2004 日本環境変異原学会
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