Assessment of the intracellular pathways modulated by rosmarinic acid and (-)-hinokinin in response to genotoxic stress

Abstract

Natural products derived-compounds (NPs) emerge as an important alternative to modulate the molecular pathways related to the genomic instability process in the early steps of carcinogenesis. Such pathways, involved in the control of proliferation by acting as regulators of cell cycle and apoptosis cell death, exhibit a rapid and coordinated action in response to genotoxic stress. Thus, the development of preventive approaches using NP requires the understanding of those pathways that effectively respond to such treatments. Rosmarinic acid (RA) and (-)- hinokinin (HNK) are NP-derived molecules that exhibited antigenotoxic activities, however, the mechanisms by which they exert their effects remain unknown. The present study aims to evaluate the chemopreventive potential of RA and HNK in vitro using different breast cancer-derived cell lines. The effects of RA and HNK on the doxorubicin-induced genotoxic stress will be evaluated considering the cellular and the molecular pathways activated in response to DNA damage. To answer these questions cell cycle kinetics, cellular proliferation and cell death will be evaluated using flow cytometry, bromodeoxyuridine colorimetric assay and cyto-morphological detection, respectively, as well as the relative quantification of gene expression by real time PCR. (AU)