title: The indolic diet-derivative, 3,3'-diindolylmethane, induced apoptosis in human colon cancer cells through upregulation of NDRG1.
abstract: N-myc downstream regulated gene-1 participates in carcinogenesis, angiogenesis, metastases, and anticancer drug resistance. In the present study, we analyzed the expression pattern of N-myc downstream regulated gene-1 following treatment of human colonic cancer cell lines; HCT-116 (well differentiated with wild-type p53 gene) and Colo-320 (poorly differentiated with mutant p53 gene), with 3,3'-diindolylmethane, a well-established proapoptotic agent product derived from indole-3-carbinol. Treatment of Colo-320 and HCT-116 with 3,3'-diindolylmethane disclosed inhibition of cell viability in a dose-dependent manner, mediated through apoptosis induction. The increased expression of N-myc downstream regulated gene-1 was detected only in poorly differentiated colon cancer cells, Colo-320 cell line. Our results suggest that N-myc downstream regulated gene-1 expression is enhanced by 3,3'-diindolylmethane in poorly differentiated cells and followed by induction of apoptosis. 3,3'-diindolylmethane induced apoptosis may represent a new regulator of N-myc downstream regulated gene-1 in poorly differentiated colonic cancer cells.
authors.affiliation: Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, Haifa 34362, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Lerner
authors.forename: M
authors.initials: M
authors.lastname: Grafi-Cohen
authors.forename: T
authors.initials: T
authors.lastname: Napso
authors.forename: N
authors.initials: N
authors.lastname: Azzam
authors.forename: F
authors.initials: F
authors.lastname: Fares
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D016588:Anticarcinogenic Agents; D018797:Cell Cycle Proteins; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C016392:3,3'-diindolylmethane