Abstract 224: Antitumorigenic effect of synthetic C-substituted diindolyl methanes originating from cruciferous vegetables in KB human oral cancer cells through endoplasmic reticulum stress

Abstract

Abstract Diindolylmethane (DIM), an isothiocyanates 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 KB human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC6H5 decreased the number of viable 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. Mechanistic studies demonstrated that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC6H5 was mediated by endoplasmic reticulum (ER) stress. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in KB cells via the ER stress pathway. This study was supported by Bio R&D program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology (M10870050003-08N7005-00311) and National Research Foundation of Korea Grant funded by the Korean Government (KRF-2008-331-E00260). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 224.