The cytotoxic effect of conjugated iron oxide nanoparticle by Papaverine on colon cancer cell line (HT29) and evaluation the expression of CASP8 and GAS6-AS1 genes

Treating chemoresistant and metastatic colon cancers faces major difficulties. Due to their high biocompatibility and magnetic property, Iron oxide nanoparticles have gained attention for the delivery of anticancer compounds. Papaverine is an alkaloid from opium that has shown anticancer properties on several cancer cells. Therefore, in this work, Iron oxide nanoparticles were conjugated with Papaverine through glucose (Glu) functionalization, and the anticancer effect of Fe3O4@Glu-Papaverine on colon cancer cells was investigated. Characterization of the synthesized NPs was confirmed by fourier-transform infrared spectroscopy (FTIR), X-Ray diffraction analysis (XRD), energy dispersive spectroscopy-mapping (EDS-Mapping), scanning electron microscopy (SEM), transmission electron microscopy (TEM), vibrating-sample magnetometer (VSM), dynamic light scattering (DLS), and zeta potential analysis. The antiproliferative effect of the nanoparticles on colon cancer cells (HT29 cell line) and normal human cells (HFF-19 cell line) was studied by (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay at 24 h. The apoptogenic property and cell cycle of nanoparticle treated cells were studied by flow cytometry by Annexin V and PI Apoptosis method. The Real-time polymerase chain reaction was used to investigate the effect of Fe3O4@Glu-Papaverine on the expression of the CASP8 and GAS6-AS1 genes by 2-ΔΔCT method. Physicochemical characterization revealed that the particles were synthesized properly, without impurities, and were in the size range of 20 to 50 nm. Also, the magnetic saturation was measured 50 emu/g. The particles were considerably more toxic for cancer cells than normal cells with IC50 values of 187 and 356 µg/mL, respectively. An increased level of cell cycle arrest at the sub-G1 phase was observed and the frequency of apoptotic cells was increased from 0.89 % to 87.2 %. Also, treating cancer cells with the nanoparticles significantly induced the CASP8 gene (3.5 folds) while attenuated the ...