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Assessment of DNA damage response pathways modulated by structuraly-modified stilbenes

Grant number: 14/12465-0
Support type:Regular Research Grants
Duration: August 01, 2014 - September 30, 2016
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Principal Investigator:Raquel Alves dos Santos
Grantee:Raquel Alves dos Santos
Home Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil
Assoc. researchers:Ana Paula de Lima Montaldi

Abstract

Genomic stability maintenance pathways represent important biological targets for developing new antineoplastic strategies. The mechanisms involved in DNA damage response (DDR) include cell cycle regulation, DNA repair and apoptosis cell death. The stilbene resveratrol is a naturally occurring compound that exerts its antitumoral activity by regulating cell proliferation and death mechanisms. Considering wide range of genetic heterogeneity in tumoral cells, the searching for more selective and satisfactory responses, especially for chemoresistant tumors, is worth of investigation and some structural modification has been proposed to resveratrol stilbene, including the replacement of hydroxyl functional groups. Such modifications can results in significant reduction of effective concentrations, improving the target-specific effects to cell death and antiproliferative responses. Therefore, considering the cellular and the molecular pathways activated in response to DNA damage, in the present study the genotoxic and antiproliferative effects of four resveratrol-derivative molecules, the (E)-4-(3,5-dimethoxystyryl)aniline (DMSA), (E) -methyl-4-(3,5-dimethoxystyril)benzoate (DMSB), (E)-1,3-dimethoxy-5-(4-methoxystyryl)benzene (EMSB) and (Z)-1,3-dimethoxy-5-(4-methoxystyryl)benzene (EMSZ) will be investigated in the breast tumoral MCF-7 and SKBR-3 cell lines and its normal counterpart MCF-10A. The cytotoxicity, genotoxicity, fraction of apoptotic cells, cell cycle kinetics, cell migration as well as gene expression will be evaluated after treatment of cell cultures with different concentrations of DMSA, DMSB, EMSB and EMSZ using XTT assay, clonogenic survival assay, bromodeoxyuridine colorimetric assay, comet assay, flow cytometry, cell migration assay as well as the quantification of gene expression by real time qPCR and Western Blot, respectively. (AU)

Scientific publications (6)
(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)
CURCINO VIEIRA, MILENA G.; BRAZ FILHO, RAIMUNDO; CURCINO VIEIRA, IVO. J. Curcinomarcoide, a Novel Limonoid From Trichilia hirta (Meliaceae)Complete H-1 and C-13 Chemical Shift Assignments. NATURAL PRODUCT COMMUNICATIONS, v. 14, n. 5 MAY 2019. Web of Science Citations: 0.
CHIBAS, LENIHER CASTAN; CINTRA, PRISCILA PAVINI; MOREIRA, MONIQUE RODRIGUES; GOULART, MIRIAN OLIVEIRA; AMBROSIO, SERGIO RICARDO; SOLA VENEZIANI, RODRIGO CASSIO; BASTOS, JAIRO KENUPP; DOS SANTOS, RAQUEL ALVES. Polyalthic Acid in Polymeric Nanoparticles Causes Selective Growth Inhibition and Genotoxicity in MCF-7 Cells. NATURAL PRODUCT COMMUNICATIONS, v. 14, n. 4 APR 2019. Web of Science Citations: 0.
CASTAN, LENIHER; DA SILVA, CRISTIANO JOSE; MOLINA, EDUARDO FERREIRA; DOS SANTOS, RAQUEL ALVES. Comparative study of cytotoxicity and genotoxicity of commercial Jeffamines (R) and polyethylenimine in CHO-K1 cells. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, v. 106, n. 2, p. 742-750, FEB 2018. Web of Science Citations: 5.
MIZUNO, CASSIA SUEMI; AMPOMAAH, WINNIFRED; MENDONCA, FERNANDA RIBEIRO; ANDRADE, GABRIELA CARVALHO; NAZARE DA SILVA, ARIEL MARIA; GOULART, MIRIAN OLIVEIRA; DOS SANTOS, RAQUEL ALVES. Cytotoxicity and genotoxicity of stilbene derivatives in CHO-K1 and HepG2 cell lines. GENETICS AND MOLECULAR BIOLOGY, v. 40, n. 3, p. 656-664, JUL-SEP 2017. Web of Science Citations: 3.
CASSIA SUEMI MIZUNO; WINNIFRED AMPOMAAH; FERNANDA RIBEIRO MENDONÇA; GABRIELA CARVALHO ANDRADE; ARIEL MARIA NAZARÉ DA SILVA; MIRIAN OLIVEIRA GOULART; RAQUEL ALVES DOS SANTOS. Cytotoxicity and genotoxicity of stilbene derivatives in CHO-K1 and HepG2 cell lines. GENETICS AND MOLECULAR BIOLOGY, v. 40, n. 3, p. -, Set. 2017.

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