title: 3,3'-Diindolylmethane suppresses growth of human esophageal squamous             cancer cells by G1 cell cycle arrest.
abstract: 3,3'-Diindolylmethane (DIM), an active metabolite of indole-3-carbinol,             is thought to have antitumor effects in experimental animals and induce apoptosis             in various cancer cells. However, the biological functions of DIM in human esophageal             cancer cells are unknown. Thus, the purpose of this study was to investigate the             cytotoxic effects of DIM in human esophageal squamous cell carcinoma (ESCC) cells             to elucidate the molecular mechanism of cell death. Three human ESCC cell lines             (TT, TE-8 and TE-12) were used to test the response to DIM. MTT, cell cycle and             western blot analyses were conducted. DIM significantly inhibited the proliferation             of ESCC cells in a dose- and time-dependent manner. The percentage of G1 phase             cells increased 48 h after being treated with DIM. DIM also reduced cyclin D1,             cyclin E2, cyclin-dependent kinase (CDK) 4 and CDK 6 activities, and increased             p15 and p27 levels. Additionally, DIM diminished pro-caspase-9 protein expression             levels and induced increased cleaved poly (ADP-ribose) polymerase levels. These             results indicate that DIM leads to G1 phase cell cycle arrest and induces apoptosis             by activating caspase-9 in ESCC cells.
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Chonbuk                     National University Medical School, Jeonju 561-180, Republic of Korea.
authors.forename: Seo Ju
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D007211:Indoles; C016392:3,3'-diindolylmethane