Abstract

Although Hydroxyurea is one of the most widely used drugs in treating breast cancer, the use of it leads to some side effects. Hence, in order to reduce complications of treatment and increase its efficiency, drug delivery has been attracted more attention. Present study included three stages. The first stage was involved in the synthesis of nanoparticles-loaded Hydroxyurea that its characteristics were evaluated by using scanning electron microscopy and Zetasizer system. In the second stage, cultured MCF-7 cells were undergone treatments by Hydroxyurea and Nanoparticles-loaded Hydroxyurea in various concentrations. In the third stage, the MCF-7 was treated by IC50 of Hydroxyurea and nanoparticles-loaded Hydroxyurea which are in combination with radiation and hyperthermia. Afterward, the viable of cell, apoptosis, and levels of caspase-8 and-9 proteins were assessed. The average size and the potential surface of nanoparticles and nanoparticles-loaded Hydroxyurea were 26 nm, 48 nm, 3.86 mV, and -29.3 mV, respectively. Results of MTT assay and apoptosis represented that the percentage of cytotoxicity in the treated groups by in combination group and nanoparticles-loaded Hydroxyurea was significantly increased in comparison with Hydroxyurea. This increase was dependent on the concentration of nanoparticles-loaded Hydroxyurea. Nevertheless, the activity of caspase-8 shows any significant changes, the activity of caspase-9 was significantly increased in the control and treatment groups. We concluded that nanoparticles-loaded Hydroxyurea and it in combination with radiation and hyperthermia induces mitochondrial-dependent apoptosis by down-regulation of caspase-8 and up-regulation of caspase-9 expressions and have higher toxicity effect on MCF-7 cells in comparison with pure Hydroxyurea.