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

• Grant number: 11/17935-7
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2011
• End date: October 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Raquel Alves dos Santos
• Grantee: Raquel Alves dos Santos
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil
• Associated researchers: Márcio Luís Andrade e Silva ; Wilson Roberto Cunha

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

UZUN, NELSON; MARTINS, THOMAS DUZZI; TEIXEIRA, GABRIELLA MACHADO; CUNHA, NAYANNE LARISSA; OLIVEIRA, ROGERIO BELLE; NASSAR, EDUARDO JOSE; DOS SANTOS, RAQUEL ALVES. Poly(L-lactic acid) membranes: Absence of genotoxic hazard and potential for drug delivery. Toxicology Letters, v. 232, n. 2, p. 513-518, JAN 22 2015. (11/21574-0, 12/01465-4, 11/17935-7)

CUNHA, NAYANNE LARISSA; TEIXEIRA, GABRIELLA MACHADO; MARTINS, THOMAS DUZZI; SOUZA, ANDERSON ROBERTO; OLIVEIRA, POLLYANA FRANCIELI; SMARO, GUILHERME VENANCIO; SOUZA REZENDE, KAREN CRISTINA; GONCALVES, NATALIA DOS SANTOS; SOUZA, DANIEL GOTTARDO; TAVARES, DENISE CRISPIM; et al. (-)-Hinokinin Induces G2/M Arrest and Contributes to the Antiproliferative Effects of Doxorubicin in Breast Cancer Cells. Planta Medica, v. 82, n. 6, p. 530-538, APR 2016. (11/17935-7)