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Determination of cellular biodistribution of Cu, Ru and Pt in human tumor and non tumor breast cells by Inductively Coupled Plasma Mass Spectrometry

Grant number: 16/23130-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): August 01, 2017
Effective date (End): August 07, 2019
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
Principal Investigator:Joaquim de Araújo Nóbrega
Grantee:Legna Andreina Colina Vegas
Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Associated scholarship(s):17/23254-9 - Quantitative determination and cellular imaging of Cu, Ru and Pt in single cells using Laser Ablation-ICP-Mass Spectrometry, BE.EP.PD


The present project focuses in the determination of low concentrations of copper, ruthenium and platinum in breast human tumor and non-tumor cells lines using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The metal complexes containing clotrimazole (CTZ) and triphenylphosphine (PPh3)ligands were synthesized and present the following formulas: [Cu(CTZ)2(PPh3)2]+, [Ru(p-cym)(CTZ)(PPh3)Cl]+ and cis-[Pt(CTZ)(PPh3)2Cl]+. Initially, will be evaluated the cytotoxic activity of the complexes against breast tumor cell line (MDA-MB-231) and non-tumor (MCF-10A), also will be determined the cell death mechanism by cycle cell analysis and apoptosis assay. Posteriorly, the cells will be treated with the complexes for the determination of total metal concentration by ICP-MS, evaluating the following parameters: time, concentration, digestion of the sample assisted by microwave radiation, using different temperatures and HNO3 concentrations. These parameters will be evaluate to optimize and establish the most efficient treatment for the samples, that will be used for the determination of metal concentration in six isolates components of the cell: cytosol, plasma membrane, nucleus, cytoskeleton, DNA and finally mitochondria. The obtained results will be compared to each other and with reported data in the literature, to better understand the sample treatment and determine the cell distribution of the metal responsible for their biological properties in order to explore their mechanisms of action.

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Scientific publications (5)
(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)
JOÃO HONORATO; KATIA M. OLIVEIRA; CELISNOLIA M. LEITE; LEGNA COLINA-VEGAS; JOAQUIM A. NÓBREGA; EDUARDO E. CASTELLANO; JAVIER ELLENA; RODRIGO S. CORREA; ALZIR A. BATISTA. “Half-Sandwich”/RuII Anticancer Complexes Containing Triphenylphosphine and p-Substituted Benzoic Acids. Journal of the Brazilian Chemical Society, v. 31, n. 11, p. 2237-2249, . (16/23130-5)
RIBEIRO, GABRIEL H.; GUEDES, ADRIANA P. M.; DE OLIVEIRA, TAMIRES D.; DE CORREIA, CAMILA R. S. T. B.; COLINA-VEGAS, LEGNA; LIMA, MAURO A.; NOBREGA, JOAQUIM A.; COMINETTI, MARCIA R.; ROCHA, V, FILLIPE; FERREIRA, ANTONIO G.; et al. Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction. Inorganic Chemistry, v. 59, n. 20, p. 15004-15018, . (16/16312-0, 16/23130-5)
COLINA-VEGAS, LEGNA; PRADO GODINHO, JOSEANE LIMA; COUTINHO, THALLITA; CORREA, RODRIGO S.; DE SOUZA, WANDERLEY; FERNANDES RODRIGUES, JULIANY COLA; BATISTA, ALZIR AZEVEDO; NAVARRO, MARIBEL. Antiparasitic activity and ultrastructural alterations provoked by organoruthenium complexes against Leishmania amazonensis. NEW JOURNAL OF CHEMISTRY, v. 43, n. 3, p. 1431-1439, . (17/23254-9, 16/23130-5)
COLINA-VEGAS, LEGNA; OLIVEIRA, KATIA M.; CUNHA, BEATRIZ N.; COMINETTI, MARCIA REGINA; NAVARRO, MARIBEL; BATISTA, ALZIR AZEVEDO. Anti-Proliferative and Anti-Migration Activity of Arene-Ruthenium(II) Complexes with Azole Therapeutic Agents. INORGANICS, v. 6, n. 4, . (17/23254-9, 16/23130-5)
REIS SILVA, HENRIQUE VIEIRA; MOREIRA DIAS, JULIA SCAFF; FERREIRA-SILVA, GUILHERME ALVARO; VEGAS, LEGNA COLINA; IONTA, MARISA; CORREA, CHARLANE CIMINI; BATISTA, ALZIR AZEVEDO; FRAZAO BARBOSA, MARILIA IMACULADA; DORIGUETTO, ANTONIO CARLOS. Phosphine/diimine ruthenium complexes with Cl-, CO, NO+, NO2-, NO3- and pyridine ligands: Pro-apoptotic activity on triple-negative breast cancer cells and DNA/HSA interactions. Polyhedron, v. 144, p. 55-65, . (16/23130-5)

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