期刊
EUROPEAN JOURNAL OF CANCER PREVENTION
卷 20, 期 5, 页码 417-425出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CEJ.0b013e32834473c3
关键词
apoptosis; C-substituted diindolylmethane; death receptor 5; endoplasmic reticulum stress; human oral cancer cell; mitochondrial membrane potential
类别
资金
- Ministry of Education, Science and Technology [2010-0007571]
- National Research Foundation of Korea [2010-0007571] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Diindolylmethane (DIM), an isothiocyanate found in cruciferous vegetables, has been shown to have cancer chemopreventive effects. A series of synthetic C-substituted DIMs (C-DIMs) analogs was developed, including DIM-C-pPhtBu and DIM-C-pPhC(6)H(5), which exhibited better inhibitory activity in cancer cells than DIM. This study examined the effects of C-DIMs on the growth of human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC(6)H(5) decreased the number of viable KB cells and induced caspase-dependent apoptosis. The apoptotic cell death was accompanied by a change in Bax/Bcl-2 ratio and damage to mitochondrial membrane potential through the induction of death receptor 5 and the cleavage of Bid and caspase 8. Studies on the mechanism of action showed that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC(6)H(5) was mediated by endoplasmic reticulum stress. In addition, C-DIMs inhibited cell proliferation and induced PARP cleavage through death receptor 5 and CHOP in HEp-2 and HN22 cells. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in human oral cancer cells through the endoplasmic reticulum stress pathway. European Journal of Cancer Prevention 20:417-425 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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