Introduction: The search of new therapeutic strategies against cancer has been focused on natural products, such as the flavonoids. In this context, our studies have shown that (-)-epicatechin (a flavonoid) present an antiproliferative effect in breast cancer cell lines. Although the action of this flavonoid in cancerous cells shows its therapeutic potential, the flavonoids are molecules with a high sensitivity to physical, chemical and biological factors that limits its activity in vivo. Aim: In this study, (-)-epicatechin-loaded chitosan nanoparticles were generated, characterized and antitumor activity was studied. The effects of these nanoparticles on ROS production and apoptosis induction in the tumour were investigated. Material and methods: Nanoparticles were prepared by the supramolecular self-assemble. The nanoparticles obtained were characterized by size, polydispersity index, Z potential and the morphology was established with transmission electron microscopy and atomic force microscopy. Antitumoral effect was evaluate in a syngeneic transplant model on BALB/c mice. ROS production in tumours was determined by the values of biomarkers of oxidative damage such as carbonyl groups, quantification of formazan by NBT’s reduction (NBT), malondialdehyde (MDA), thiobarbituric reactive substance (TBARS), also the activity of glutathione peroxidase (GSH-Px) was analyzed. Finally, DNA fragmentation assay was performed to determine the induction of apoptosis. Results: Nanoparticles with size less to 200 nm were obtained, with a polydispersity index of 0.2, a zeta potential between -18 mV and -33 mV and spherical morphology. Interestingly, nanoparticles of (-)-epicatechin-loaded chitosan showed a high antitumor activity in comparison to the others study groups. Finally, the differences in biomarkers of oxidative damage (MDA, TBARS and NBT) and decreasing of GSH-Px activity were observed in tumours of mice treated with nanoparticles of (-)-epicatechin-loaded chitosan. Conclusions: The data obtained in this study, suggest that the antitumor activity of nanoparticles (-)-epicatechin-loaded chitosan is mediated by an induction of apoptosis and increase in the production of ROS.

Nanoparticles (-)-epicatechin-loaded chitosan induced apoptosis in breast cancer: in vivo and in vitro study

254th National Meeting (2017)

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