title: The anticancer effects of desferrioxamine on human breast adenocarcinoma and hepatocellular carcinoma cells.
abstract: N-myc downstream-regulated gene 1 (NDRG1) is defined as metastasis suppressor and can be downregulated in many types of cancers, and reported to be an indication of tumor progression in hepatocellular carcinomas. Several in-vivo and in-vitro studies have demonstrated that iron chelators such as Desferrioxamine (DFO) and 1-10 Phenanthroline (PHEN) are effective antitumor agents. It is suggested that these chelators deliver their antitumor activity by acting on the NDRG1 gene expression. It remains unclear why NDRG1 gene expression affects the tumors differently, or becomes affected differently. We consider that this different effect might be caused by variants. Based on this information, we developed specific primers and probes for NDRG1 mRNA variants using bioinformatics analysis, and investigated how DFO and PHEN affected the dynamics of NDRG1 variant on the cell lines of Human Breast Adenocarcinoma (MCF-7) and Hepatocellular Carcinoma (HepG2) that demonstrate opposite action for the relationship NDRG1-metastasis. We administrated various doses of DFO and PHEN into the cells to monitor cell vitality and proliferation with Real time Cell Analyzer. We analyzed the gene expression levels of study groups with Quantitative RT-PCR as well as relative gene expression. Variants of NDRG1 mRNA were transcriptionally regulated after HepG2 and MCF-7 cells were treated by iron chelators, resulting in domination of NDRG1 mRNA Variant 1 (V1) in the HepG2 calls and domination of NDRG1 mRNA Variant 2 (V2) in the MCF-7 cells. Anti-proliferative and cytotoxic effects were observed in the MCF-7 cells whereas an increased proliferation was present in the HepG2 cells.
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Osman
authors.initials: O
authors.lastname: Salis
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Abdulkerim
authors.initials: A
authors.lastname: Bedir
authors.affiliation: Department of Medical Biochemistry, Trabzon Public Health Laboratory, Trabzon, Turkey.
authors.forename: Veli
authors.initials: V
authors.lastname: Kilinc
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Alacam
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Sedat
authors.initials: S
authors.lastname: Gulten
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Okuyucu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D003676:Deferoxamine / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000096:biosynthesis; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D003676:Deferoxamine; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D000099259:N-myc Downstream-Regulated Gene 1 Protein
keywords: N-myc downstream-regulated gene 1; desferrioxamine; human breast adenocarcinoma and hepatocellular carcinoma