title: 3,3'-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically kills cancer cells without destroying the majority of healthy cells. However, numerous types of cancer cell, including gastric cancer cells, tend to be resistant to TRAIL. The bioactive product 3,3'-diindolylmethane (DIM), which is derived from cruciferous vegetables, is also currently recognized as a candidate anticancer agent. In the present study, a Cell Counting Kit 8 cell growth assay and an Annexin V-fluorescein isothiocyanate apoptosis assay were performed to investigate the potentiating effect of DIM on TRAIL-induced apoptosis in gastric cancer cells, and the possible mechanisms of this potentiation. The results obtained demonstrated that, compared with TRAIL or DIM treatment alone, co-treatment with TRAIL (25 or 50 ng/ml) and DIM (10 µmol/l) induced cytotoxic and apoptotic effects in BGC-823 and SGC-7901 gastric cancer cells. Furthermore, western blot analysis revealed that the protein expression levels of death receptor 5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were upregulated in the co-treated gastric cancer cells. To the best of our knowledge, the present study is the first to provide evidence that DIM sensitizes TRAIL-induced inhibition of proliferation and apoptosis in gastric cancer cells, accompanied by the upregulated expression of DR5, CHOP and GRP78 proteins, which may be involved in endoplasmic reticulum stress mechanisms.
authors.affiliation: Department of Preventive Medicine, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China ; Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China ; Department of Health Care, The Fourth Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
authors.forename: Shuhan
authors.initials: S
authors.lastname: Miao
authors.affiliation: Department of Preventive Medicine, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Preventive Medicine, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China ; Department of Public Health Laboratory Science, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Rongzhu
authors.initials: R
authors.lastname: Lu
keywords: 3,3′-diindolylmethane; apoptosis; endoplasmic reticulum stress; gastric cancer; tumor necrosis factor-related apoptosis-inducing ligand