期刊
EUROPEAN JOURNAL OF CANCER PREVENTION
卷 19, 期 2, 页码 153-159出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CEJ.0b013e328333d088
关键词
apoptosis; Bcl-2; 5,5 '-dibromodiindolylmethane; human oral squamous carcinoma cells; mitochondrial membrane potentials; p38 mitogen-activated protein kinase
类别
资金
- Korean Government (MOEHRD) [KRF-2008-331-E00260]
- Chonbuk National University
Cruciferous vegetables contain isothiocyanates including diindolylmethane (DIM) that exhibit cancer chemopreventive effects. We developed a series of synthetic ring-substituted DIM analogs including 5,5'-dibromoDIM that exhibited better inhibitory activity in breast and colon cancer cells than DIM. In this study, we investigated whether 5,5'-dibromoDIM inhibits the proliferation of KB and YD-10B oral squamous carcinoma cell lines. 5,5'-dibromoDIM decreased the cell survival and inhibited the growth of oral cancer cells. Exposure of KB and YD-10B cells to 5,5'-dibromoDIM induced caspase-dependent apoptosis evidenced by poly-ADP ribose polymerase cleavage, accumulation of sub-G(1) population, and nuclear condensation and fragmentation. In addition, apoptotic cell death was correlated with damage to the mitochondrial membrane potential through a decrease in the level of Bcl-2 protein expression. Mechanistic studies showed that mitochondria-dependent apoptosis induced by 5,5'-dibromoDIM was mediated by the p38 mitogen-activated protein kinase pathway but not the ERK1/2 and JNK pathway. These results highlight 5,5'-dibromoDIM as an important chemopreventive agent for the clinical treatment of oral cancer through the p38 mitogen-activated protein kinase pathway. European Journal of Cancer Prevention 19: 153-159 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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