Effects of Iron oxide functionalized by Glutamic acid and 2-pyridinecarboxaldehyde thiosemicarbazone against lung cancer A549 cells and analysis of NDRG1 gene expression

Background: Lung cancer is a disease with high mortality rate that conventional drug treatments have not been successful in controlling it. The activity of iron chelators in various studies has been considered by scientists as a new treatment strategy. The primary objective of this study was to synthesize a novel Fe3O4 thiosemicarbazone complex and investigate its anti-proliferative activity against A549 cells of lung cancer. Methods: This experimental study was carried out in Islamic Azad University of Rasht Branch, from September of 2018 to September 2019. First thiosemicarbazone (PTSC) was synthesized by the method of the condensation reaction of amine and aldehyde groups. Also, the Fe3O4 nanoparticulates were synthesized using the co-precipitation method in the presence of glutamic acid. Then, Fe3O4@Glu complex functionalized with bio-reactive PTSC moiety. Besides, morphological characteristics of Fe3O4@Glu/PTSC complex were determined by scanning electron microscope (SEM) images. The cell viability was detected in 62.5, 125, 250, 500, and 1000 µg/ml for treated cells with Fe3O4@Glu/PTSC complex via MTT assay. Changes of NDRG1 gene expression the level in treated cells were investigated via qRT-PCR analysis. Therefore, total RNA was extracted after culturing the cells and cDNA of NDRG1 and GAPDH genes as the study and control gene was obtained, respectively. Ultimately, the level of NDRG1 gene expression was compared with level of GAPDH mRNA expression via the 2– ΔΔCt method. Results: SEM images confirmed the sphericality of the Fe3O4 @ Glu / PTSC complex. The size of the nanoparticles was uniform and about 52-23 nm. The cell survival assay (MTT) results revealed the anti-proliferative properties of this complex in a dose-dependent manner (IC50=135.6 µM/ml). In treated cells, the gene expression of NDRG1 was 1.8-fold higher after 12 h. However, after 24 hours of incubation, this gene was showed a 0.67-fold decrease in expression compared to the control group. Conclusion: The results of the present study suggest that Fe3O4@Glu/PTSC nanoparticulates by a decrease of NDRG1 expression, exhibit effective anti-cancer activity against lung cancer cells.