Tocopherol-loaded niosomes: a promising nanocarrier for enhancing apoptotic and anti-metastatic effects in breast cancer cells

Vollständiger Abstract

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Abstract Background Breast cancer is (BC) considered as one of the most common causes of morbidity and mortality among women worldwide. Tocopherol (Vitamin E) is a strong lipid soluble antioxidant, which has anticancer effects but its therapeutic application is limited due to poor water solubility. The aim of this study was to fabricate tocopherol-niosome nanoparticles (NPs) and determined their cytotoxic, apoptotic and anti-metastatic properties in human breast cancer MCF-7 cell line. Materials and methods The thin-film hydration method was used to prepare tocopherol loaded niosomes, which were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential analysis, and Fourier transform infrared spectroscopy (FTIR). The MTT assay was used to determine cytotoxicity. Flow cytometry was used to analyze apoptosis and cell cycle distribution. A wound-healing assay was tested to evaluate the anti-migratory effect. Real-time PCR was used to determine the gene expression levels of Bax , BCL-2 , P53 and MMP2 in MCF-7 and normal MCF-10 cells. Results The results showed that the synthesized NPs had spherical geometry and average size of 61.5 nm with colloidal stability. The IC 50 of synthesized NPs was reported to be 0.0125 mg/mL, which was significant different from free tocopherol. Flow cytometry results showed that the total apoptosis rate in the tocopherol-niosomes group was 81%, which was significant compared to the free tocopherol group of 27%. Gene expression analysis showed that pro-apoptotic Bax and P53 genes were significantly upregulated and anti-apoptotic BCL-2 and metastatic marker MMP2 were downregulated in MCF-7 cells with insignificant changes in normal MCF-10 cells. Also, tocopherol that was loaded into niosomes greatly suppressed the migration of cancerous cells. Conclusion Niosome-tocopherol complex significantly increases cytotoxicity, induction of apoptosis and anti-metastatic effect against breast cancer cells, which validates their role as a useful nanocarrier to treat breast cancer.