Relative quantification of DNA-Topoisomerases enzymes in cell lines: Correlation between cytotoxicity and mechanism of action of coordination compounds

• Grant number: 19/11242-1
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2019
• End date: July 31, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Fillipe Vieira Rocha
• Grantee: Fillipe Vieira Rocha
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

DNA-topoisomerases enzymes are one of main biological targets against cancer. These proteins participate of different nuclear processes. Literature shows that some types of cancer have a great expression of the topoisomesae I² (TOPO1B) and/or topoisomesae II± (TOPO2A). However, few studies were performed to prove the quantities of the enzymes inside the cells. Thus, this Project has the objective to determine the relative quantities of the topoisoemrases enzymes by Western Blot e ELISA methodologies in different cells lines: MDA-MB-231 (metastatic breast cancer), MCF7 (breast cancer), DU 145 (prostate cancer), A549 (lung cancer), A2780cis (cisplatin-resistant ovary cancer), MCF10A (non-tumoral breast), PNT2 (non-tumoral prostate), MCR5 (non-tumoral lung). Additionally, we intend to synthesize, characterize and evaluate the cytotoxicity and the capacity to inhibit the action of TOPO1B and TOPO2A of a large number of coordination compounds with different metal ions (Pd2+, Pt2+ e Ag+). A deep investigation of mechanism of action of the most promising compounds will be making by cell cycle arrest and apoptosis assays. To determine the concentration of metal íon inside the cellular media ICP-MS analysis would be performed. Therefore, we expect that these results help us to explain experimentally the relationship between the expressions of the enzymes, cytotoxicity and mechanism of action. Indeed, our works will achieve another scientific level. (AU)

Scientific publications

(8)

(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)

PERECIN, CAIO J.; TIRICH, BEATRIZ M.; NAGAMINE, LUIZ C. C. M.; PORTO, GABRIELA; V. ROCHA, FILLIPE; CERIZE, NATALIA N. P.; VARANDA, LAUDEMIR C.. Aqueous synthesis of magnetite nanoparticles for magnetic hyperthermia: Formation mechanism approach, high water-dispersity and stability. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 627, OCT 20 2021. (20/06501-5, 19/11242-1, 16/21371-5, 13/01284-2)

CORDEIRO JUNIOR, PAULO JORGE MARQUES; SOUTO, ROBSON SILVA; ALMEIDA, MICHELL DE OLIVEIRA; PEREIRA, GEORGE BUENO SANTANA; FRANCO, MARIANE ARAUJO; HONORIO, KATHIA MARIA; ROCHA, FILLIPE VIEIRA; LANZA, MARCOS ROBERTO DE VASCONCELOS. A combined approach toward enhancing 2-electron oxygen reduction through the incorporation of Pd-based complex into a carbonaceous matrix: Experimental and mechanistic-theoretical studies. Electrochimica Acta, v. 460, p. 13-pg., 2023-05-20. (16/19612-4, 14/50945-4, 18/19103-8, 19/11242-1, 17/10118-0, 22/02876-0)

MARQUES CORDEIRO-JUNIOR, PAULO JORGE; MARTINS, ALYSSON STEFAN; SANTANA PEREIRA, GEORGE BUENO; ROCHA, FILLIPE VIEIRA; RODRIGO RODRIGO, MANUEL ANDRES; DE VASCONCELOS LANZA, MARCOS ROBERTO. Bisphenol-S removal via photoelectro-fenton/H2O2 process using Co-porphyrin/Printex L6 gas diffusion electrode. Separation and Purification Technology, v. 285, p. 13-pg., 2022-03-15. (20/13088-7, 19/11242-1, 17/10118-0, 16/04201-9, 14/50945-4, 16/01937-4, 17/13123-4, 16/19612-4)

DE MOURA, THALES REGGIANI; ZANETTI, RENAN DIEGO; SILVA, DEBORA EDUARDA SOARES; DE FARIAS, RENAN LIRA; MAURO, ANTONIO EDUARDO; PEREIRA, JOSE CLAYSTON MELO; DE SOUZA, ALINE APARECIDA; DA SILVA SIQUEIRA, FABIO; DE SOUZA JUDICE, WAGNER ALVES; LIMA, MAURO ALMEIDA; et al. Palladium(ii) complexes bearing 1-iminothiolate-3,5-dimethylpyrazoles: synthesis, cytotoxicity, DNA binding and enzymatic inhibition studies. NEW JOURNAL OF CHEMISTRY, v. 44, n. 45, p. 19891-19901, DEC 7 2020. (15/12098-0, 16/25112-4, 14/02205-1, 09/54011-8, 19/11242-1, 16/17711-5)

HOOPER, CATHERINE A. J.; CARDO, LUCIA; CRAIG, JAMES S.; MELIDIS, LAZAROS; GARAI, ADITYA; EGAN, ROSS T.; SADOVNIKOVA, VIKTORIIA; BURKERT, FLORIAN; MALE, LOUISE; HODGES, NIKOLAS J.; et al. Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding. Journal of the American Chemical Society, v. 142, n. 49, p. 20651-20660, DEC 9 2020. (19/11242-1)

LIMA, MAURO ALMEIDA; COSTA, VINICIUS A.; FRANCO, MARIANE ARALIJO; DE OLIVEIRA, GABRIELA P.; DEFLON, VICTOR M.; ROCHA, FILLIPE VIEIRA. Palladium(II) complexes bearing thiosemicarbazone and phosphines as inhibitors of DNA-Topoisomerase II enzyme: Synthesis, characterizations and biological studies. Inorganic Chemistry Communications, v. 112, FEB 2020. (16/04201-9, 19/11242-1)

CORDEIRO, PAULO JORGE MARQUES; MARTINS, ALYSSON STEFAN; PEREIRA, GEORGE BUENO SANTANA; ROCHA, FILLIPE VIEIRA; RODRIGO, MANUEL ANDRES RODRIGO; LANZA, MARCOS ROBERTO DE VASCONCELOS. High-performance gas-diffusion electrodes for H2O2 electrosynthesis. Electrochimica Acta, v. 430, p. 11-pg., 2022-08-29. (14/50945-4, 19/11242-1, 16/04201-9, 17/10118-0, 20/13088-7, 17/13123-4, 16/19612-4, 16/01937-4)

AKINYEMI, AMOS O.; PEREIRA, GEORGE B. S.; OLIVEIRA, GABRIELA P.; LIMA, MAURO A.; ROCHA, JOSIAS S.; COSTA, VINICIUS A.; FORTALEZA, DARIO B.; TEIXEIRA, TAMARA; ZANOTTI, KARINE; FORIM, MOACIR ROSSI; et al. Palladium (II) complexes as inhibitors of cathepsin B and topoisomerase I beta: Synthesis, characterization, and cytotoxicity. Journal of Molecular Structure, v. 1294, p. 14-pg., 2023-12-15. (19/11242-1, 21/04876-4, 22/02876-0)