Anticancer activity and modulation of protein and gene expression by baicalein loaded iron oxide nano conjugates in triple negative breast cancer cells

Abstract

The present study was carried out with the aim of analyzing the anticancer activity of baicalein loaded newlineiron oxide nanoparticles, against the triple negative breast cancer cells, MDA-MB-231, and to understand newlineits mechanism of action. The work was carried out in four distinct phases. In the first phase, iron oxide, newlinebaicalein and baicalein loaded iron oxide nanoparticles were synthesized by co-precipitation method and newlinecharacterized by various spectroscopic methods. In phase II, drug releasing profile, loading and newlineencapsulation efficiency, cellular internalization and nuclear localization of baicalein loaded iron oxide newlinenanoconjugates were assessed. In phase III, in order, to optimize the dose of synthesized iron oxide newlinenanoparticles in both the non-cancerous and cancerous cell lines, dose and time-dependent response newlinestudies were carried out. In phase IV, the baicalein iron nanoconjugates induced cell death, events of cell newlinecycle, mitochondrial membrane potential were studied by using flow cytometry and the expression of newlinepro-apoptotic and anti-apoptotic protein and genes were studied by Western blotting and semi newlinequantitative RT-PCR. The expression profile of 84 genes, which are associated with breast cancer newlineprogression, was studied using Breast Cancer Real time PCR array. The results of phase I, confirmed that newlinethe synthesized material was iron oxide nanoparticles (Fe2O3) and also confirmed that materials were newlinehighly stable, monodispersive, crystalline and spherical in nature and the surfactant molecule PEG and newlinebaicalein were firmly attached to the surface of synthesized particles. The results of phase II revealed that newlinethe drug releasing profile released maximum amount of baicalein in acidic pH 5.5. Synthesized baicalein newlineiron nanoconjugates were localized in various cellular organelles of the treated cells and nuclear newlinelocalization was also confirmed by confocal microscopy. The results of phase III, showed that synthesized baicalein iron nanoconjugates showed significant toxicity in triple negative breast cancer cells