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.

Iron and Copper Intracellular Chelation as an Anticancer Drug Strategy

“…DFO is clinically used for the treatment of Fe overload and was the first Fe chelator to be tested for anticancer applications [158]. It inhibits melanoma and hepatoma cell growth both in vivo and in vitro by blocking their proliferation in the S phase of the cell cycle [159]. The mechanism of DFO in hepatocellular carcinoma cell lines (HCC) was investigated by monitoring Tf- 59 Fe uptake in the cells [160].…”

SECONDARY BIOACTIVE METABOLITE GENE CLUSTERS IDENTIFICATION OF ANTICANDIDA-PRODUCING Streptomyces Sp. GMR22 ISOLATED FROM WANAGAMA FOREST AS REVEALED BY GENOME MINING APPROACH

“…Desferrioxamine B is an iron chelator, which has a variety of clinical applications for patients with iron overload in terms of improving the quality of life and overall survival. In addition, Desferrioxamin B in the experiment showed potential anticancer in the cells of colon cancer (Salis et al, 2014).…”

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

“…As a result, a variety of them have been synthesized (e.g. deferiprone; DFP [18], desferrioxamine; DFO [19], tachpyridine [20], triapine [21] and 2-hydroxy-1-naphthyl aldehyde isonocitinyl hydrazine [22]) all of which are capable of acting as anticancer agents (Fig. 1a).…”