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

Grant number: 16/07729-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2016
Effective date (End): July 31, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Carmen Silvia Passos Lima
Grantee:Tuany Zambroti Cândido
Home 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)

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Scientific publications
(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)
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, . (19/16904-2, 16/07729-4, 12/50191-4)
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, . (18/13588-0, 16/07729-4, 17/12719-0)
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, . (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)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.

Filed patent(s) as a result of this research project

PROCESSO DE OBTENÇÃO DOS DISPOSITIVOS DE CB-AG-NMS E CB-AG-PABA, DISPOSITIVOS DE CB-AG-NMS E CB-AG-PABA E USO DOS DISPOSITIVOS CB-AG-NMS E CB-AG-PABA BR1020190223731 - Associação São Bento de Ensino (UNIARA) ; Universidade Estadual de Campinas (UNICAMP) . TUANY ZAMBROTI CÂNDIDO ; RAPHAEL ENOQUE FERRAZ DE PAIVA ; SILMARA CRISTINA LAZARINI FRAJÁCOMO ; DOUGLAS HIDEKI NAKAHATA ; NAYARA APARECIDA SIMEI AQUARONI ; CARMEN SILVIA PASSOS LIMA ; PEDRO PAULO CORBI ; Wilton Rogério Lustri ; ANA LUCIA TASCA GOIS RUIZ ; KARIN MAIA MONTEIRO ; JOÃO ERNESTO DE CARVALHO ; CAMILLA ABBEHAUSEN - October 2019, 24