Chrysin loaded nanostructured lipid carriers (NLCs) triggers apoptosis in MCF-7 cancer cells by inhibiting the Nrf2 pathway

Abstract

We investigated the role of chrysin as an effective adjuvant along with nanostructured lipid carriers (NLCs) to increase the cytotoxicity of doxorubicin (Dox) in MCF-7 breast cancer cells. The prepared formulation was characterized from point of view scanning electron microscope (SEM), size & zeta potential. Cellular uptake and cytotoxicity of nanoparticles were examined by fluorescent microscopy and MTT assay, respectively. Flow cytometry and real-time PCR were used to understand the molecular mechanism of Nrf2 and related downregulating genes. The average size of the nanoparticles was 105 +/- 2 nm, which was confirmed by SEM. Our results demonstrated that incubation of the cells with chrysin-loaded NLCs enhanced the percentage of apoptosis from 21.11 +/- 5.72% to 27 +/- 3.13% (p < 0.05). Furthermore, the population of cancer cells in the sub-Gi phase increased up to 12 +/- 2.1% compared to untreated cells (p < 0.05). mRNA expression levels of Nrf2, NQO1, 1101, and MRP1 exhibited a significant decrease compared to the control group (p < 0.05). Our findings recommend that chrysin delivery along with NLCs would enhance the efficacy of Dox by exerting inhibitory effects against drug efflux pumps and drug detoxification enzymes.