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

• Grant number: 14/12465-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2014
• End date: September 30, 2016
• 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: 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

(7)

(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)

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. (14/12465-0)

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. (14/12465-0)

CASTAN, L.; DA SILVA, C. J.; DOS SANTOS, R.; MOLINA, E.. Comparative study of cytotoxicity and genotoxicity of commercial Jeffamines((R)) and polyethylenimine in CHO-K1 cells. Toxicology Letters, v. 259, p. 1-pg., 2016-10-01. (14/12465-0)

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. 9-pg., 2017-07-01. (14/12465-0)

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. (11/13630-7, 14/12465-0)

GONCALVES, NATALIA DOS SANTOS; SILVA PEREIRA DE MELLO, TAMIRES MARIA; MIZUNO, CASSIA SUEMI; HAIDER, SAQLAIN; DOS SANTOS, RAQUEL ALVES. Cis-trimethoxystilbene, exhibits higher genotoxic and antiproliferative effects than its isomer trans-trimethoxystilbene in MCF-7 and MCF-10A cell lines. GENETICS AND MOLECULAR BIOLOGY, v. 44, n. 3, 2021. (18/16461-0, 14/12465-0)

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. (11/13630-7, 14/12465-0)