Evaluating the Anti-cancer effect of curcumin loaded on pegylated niosome nanoparticles through expression GPR75 in cancer colorectal cell line

Abstract

GPR75 is a special member of the family of G protein-coupled receptors (GPCRs), which has attracted the attention of scientists in recent years. In a recent study, the relationship between GPR75 expression and obesity was found, and other studies also found a significant relationship between obesity and cancer. Curcumin is a yellow compound obtained from a plant with the scientific name Curcuma longa, which has been proven to have anti-cancer properties. The loading of curcumin in nanoparticles such as niosomes increases the anticancer effects of drugs due to enhanced solubility and proper release of the drugs at the target site. The purpose of the upcoming study is to evaluate the anticancer effect of curcumin loaded in pegylated niosome nanoparticles on human colorectal Caco-2 cells and its effect on GPR75 receptor expression. Materials and methods: Curcumin-loaded PEGylated niosomal nanoparticles were synthesized, and their physicochemical properties were investigated using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and dynamic light scattering (DLS). The release rate of the drug loaded from the nanoparticles was measured by placing the nanoparticles containing the drug in the release medium. To investigate the toxicity effect of Curcumin-loaded PEGylated niosomal nanoparticles on the Caco-2 cell line, an MTT assay was performed. An apoptosis assay was performed to evaluate the effect of drug on the programmed death of Caco-2 cells. The effect of drug on cell cycle arrest was investigated using a cell cycle assay. Finally, the expression levels of hTERT, Cyclin D1, GPR75, Caspase-3, and Caspase-7 genes were investigated using Real-Time PCR in the presence of Curcumin-loaded PEGylated niosomal nanoparticles and free-curcumin.

Results: Microscopic findings and FT-IR results showed successful drug loading. Also, the efficiency of drug encapsulation, determined the entrapment efficiency of curcumin in niosomes being 83.7%. The results of the MTT assay indicated a significant cell growth arrest compared to the control group. Pharmacotoxicity evaluation demonstrated that curcumin loaded in pegylated niosomes had more toxic effects than in its free state, in a dose-dependent manner. Real-time PCR results showed that curcumin, both in its free form and when loaded in nanoparticles, inhibits the expression of the hTERT, Cyclin D1, and GPR75 genes while increasing the expression of Caspase-3 and Caspase-7 genes. Treatment of cells with drugs loaded in pegylated niosomes resulted in a greater effect on the expression of these genes. The results of the apoptosis test showed that the percentage of living cancer cells treated with free curcumin and curcumin encapsulated in nanoparticles was 51.2% and 24.6%, respectively. Furthermore, the death of cells in the presence of curcumin-loaded PEGylated niosomal nanoparticles was more pronounced, and the type of late apoptotic.