The p38 MAPK pathway is critical for 5,5 '-dibromodiindolylmethane-induced apoptosis to prevent oral squamous carcinoma cells
- Authors
- Choi, Kyeong-Hee; Kim, Hyung-Kook; Kim, Jun-Hee; Choi, Eun-Sun; Shin, Ji-Ae; Lee, Syng-Ook; Chintharlapalli, Sudhakar; Safe, Stephen; Abdelrahim, Maen; Kong, Gu; Choi, Hong Seok; Jung, Ji-Youn; Cho, Hyun-Tae; Cho, Nam-Pyo; Cho, Sung-Dae
- Issue Date
- Mar-2010
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- apoptosis; Bcl-2; 5,5 ' -dibromodiindolylmethane; human oral squamous carcinoma cells; mitochondrial membrane potentials; p38 mitogen-activated protein kinase
- Citation
- EUROPEAN JOURNAL OF CANCER PREVENTION, v.19, no.2, pp.153 - 159
- Indexed
- SCIE
SCOPUS
- Journal Title
- EUROPEAN JOURNAL OF CANCER PREVENTION
- Volume
- 19
- Number
- 2
- Start Page
- 153
- End Page
- 159
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/175358
- DOI
- 10.1097/CEJ.0b013e328333d088
- ISSN
- 0959-8278
- Abstract
- 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.
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