title: Chemopreventive effects of synthetic C-substituted diindolylmethanes originating from cruciferous vegetables in human oral cancer cells.
abstract: 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-pPhC6H5, 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-pPhC6H5 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-pPhC6H5 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.
authors: Department of Oral Pathology, School of Dentistry, Chonbuk National University, Republic of Korea.
authors: Ji-Ae
authors: JA
authors: Shin
authors: Jung-Hyun
authors: JH
authors: Shim
authors: Eun-Sun
authors: ES
authors: Choi
authors: Dae-Ho
authors: DH
authors: Leem
authors: Ki Han
authors: KH
authors: Kwon
authors: Syng-Ook
authors: SO
authors: Lee
authors: Stephen
authors: S
authors: Safe
authors: Nam-Pyo
authors: NP
authors: Cho
authors: Sung-Dae
authors: SD
authors: Cho