Iron Oxide Nanoparticles Conjugated to Thiosemicarbazone Reduce the Survival of Cancer Cells by Increasing the Gene Expression of MicroRNA let-7c in Lung Cancer A549 Cells.

Abstract

Cancer cells have a higher demand for iron to grow and proliferate. A new complex of iron nanoparticles and thiosemicarbazones was synthesized. Confirmation tests included UV-visible, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared (FTIR), X-ray diffraction (XRD) and zeta potential. MTT assay, flow cytometry and qRT-PCR were used to investigate anti-proliferative effect, amount of apoptosis and the effect of Fe3 O4 @Glu/BTSC on changes in gene expression of microRNA let-7c (let-7c), respectively. The specifications of Fe3 O4 @ Glu/BTSC were confirmed at 5 nm. Fe3O4@Glu/BTSC was more effective than BTSC and Fe3 O4 on A549 cells (IC50=166.77 µg/mL) but its effect on healthy cells was smaller (CC50=189.15 µg/mL). The drug selectivity index (SI) was calculated to be 1.13. The initial apoptosis rate was 46.33% for Fe3 O4 @Glu/BTSC, 28.27% for BTSC and 26.02% for Fe3 O4 . BTSC and BTSC@Fe3 O4 inhibited the cell cycle progression in the Sub-G1 and S phases. let-7c expression was 6.9 times higher in treated cells compared to the control group. The expression rate was 2.2 with BTSC compared to the control group and 1.6 times for Fe3 O4. Fe3 O4 @Glu/BTSC has proper anti-proliferative effects against lung cancer cells by increasing the expression of let-7c and inhibiting the cell cycle with the apoptosis activation pathway.