Metal complex from golden, palladium and silver in the treatment of skin squamous cell carcinoma

• Grant number: 16/07729-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2016
• End date: July 31, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carmen Silvia Passos Lima
• Grantee: Tuany Zambroti Cândido
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The metals and their compounds were used empirically in the treatment of diseases for a long time. A continuous effort of the scientific community is dedicated to the search for new compounds with antitumor activity, including metallodrugs. Skin tumors are the most common worldwide, including squamous cell carcinoma (CCEP). The only curative therapy for tumor patients is surgical resection, with potential aesthetic or functional abnormalities to patients, since in most cases, tumors develop on the face and other exposed parts of the body. Thus, the therapeutic discovery that reduce tumor size for subsequent resection, neoadjuvant said, are very important as they may reduce morbidity attributed to surgical treatment. Researchers in our group synthesized and characterized new complexes containing gold, palladium and silver as potential anticancer agents. The aim of this study is to evaluate the effects of metal complexes [Au (MTZ) CN], [R3PAuL] +, [Pd (C6H10NO2S) 2] and(Ag-NMS) as an antitumor agent in the ECPC. Initially, the antitumor effect of each compound is evaluated in ten different strains of tumor cells and a line normal keratinocytes to test the sulforhodamine B. Then, the best effects of the two compounds selected from experiments with cell lines will be assessed ECPC cultures of 40 patients who underwent surgical resection of the tumor, with the test of sulforhodamine B. the mechanisms of action of the two best selected compounds of experiments with cell lines will be investigated in tumor cell lines by flow cytometry with annexin markers , multicaspases and caspases. of the selected compounds permeation studies will be performed in Franz diffusion cells. Finally the effects and toxicities topical (bacterial cellulose sticker) of the top two compounds are evaluated in 68 mice (with CCEP induced by daily administration of DMBA / TPA and controls) by the clinical analysis of tumor animals and dimensions and histological evaluations of organs. Differences between groups will be calculated according to the Dunnett's method for parametric ANOVA and methods, in which all samples are compared with controls. We believe that the results of the study may help identify new active drugs in ECPC by topical administration and in the near future, they can be used in clinical studies in tumor patients by our research group. (AU)

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)

SIMEI AQUARONI, NAYARA AP.; NAKAHATA, DOUGLAS H.; LAZARINI, SILMARA C.; RESENDE, FLAVIA A.; CANDIDO, AMANDA L. P.; BARUD, HERNANE DA SILVA; CLARO, AMANDA MARIA; DE CARVALHO, JOAO ERNESTO; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; et al. Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support. Journal of Inorganic Biochemistry, v. 212, NOV 2020. (17/19243-1, 15/09833-0, 17/16278-9, 18/12062-4, 16/07729-4, 13/07276-1, 18/12590-0, 18/25512-8, 14/06779-2, 19/03049-7, 18/02344-2, 18/00163-0, 15/20882-3)

TELES, C. M.; LAMMOGLIA, L. C.; JULIANO, M. A.; RUIZ, A. L. T. G.; CANDIDO, T. Z.; DE CARVALHO, J. E.; LIMA, C. S. P.; ABBEHAUSEN, C.. Novel anticancer Pd-II complexes: The effect of the conjugation of transferrin binding peptide and the nature of halogen coordinated on antitumor activity. Journal of Inorganic Biochemistry, v. 199, OCT 2019. (17/12719-0, 18/13588-0, 16/07729-4)

CANDIDO, TUANY ZAMBROTI; FERRAZ DE PAIVA, RAPHAEL ENOQUE; FIGUEIREDO, MARIANA CECCHETTO; COSER, LILIAN DE OLIVEIRA; LAZARINI FRAJACOMO, SILMARA CRISTINA; ABBEHAUSEN, CAMILLA; CARDINALLI, IZILDA APARECIDA; LUSTRI, WILTON ROGERIO; CARVALHO, JOAO ERNESTO; TASCA GOIS RUIZ, ANA LUCIA; et al. Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment of Skin Squamous Cell Carcinoma. PHARMACEUTICS, v. 14, n. 2, p. 18-pg., 2022-02-01. (16/07729-4, 18/12062-4, 15/09833-0, 17/12719-0, 18/12590-0)

TELES, CATHERINE M.; ANTUNES, VICTOR U.; CARDOSO, RAQUEL S.; CANDIDO, TUANY Z.; LIMA, CARMEN S. P.; RUIZ, ANA LUCIA T. G.; JULIANO, MARIA A.; FAVARO, DENIZE C.; ABBEHAUSEN, CAMILLA. Functionalization of new anticancer Pt(II) complex with transferrin receptor binding peptide. Inorganica Chimica Acta, v. 511, OCT 1 2020. (19/16904-2, 16/07729-4, 12/50191-4)

CANDIDO, TUANY ZAMBROTI; TASCA GOIS RUIZ, ANA LUCIA; TINTI, SIRLENE VALERIO; ABBEHAUSEN, CAMILLA; CORBI, PEDRO PAULO; DE CARVALHO, JOAO ERNESTO; PASSOS LIMA, CARMEN SILVIA. Antiproliferative screening of Gold, Palladium and Silver Metallic Complexes. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, v. 22, p. 1-pg., 2017-07-01. (16/07729-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CÂNDIDO, Tuany Zambroti. Metal complexes of gold, palladium and silver in the treatment of squamous skin cells. 2019. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.