Metal complexes of gold, palladium and silver in the treatment of squamous skin cells

Author(s)

Tuany Zambroti Cândido

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2019-07-24

Examining board members

Carmen Silvia Passos Lima; José Augusto Rinck Júnior; Renata Ferreira Magalhães; Marco Vinícius Chaud; Rogério Heládio Lopes Motta

• Advisor: Carmen Silvia Passos Lima; João Ernesto de Carvalho

Abstract

Skin squamous cell carcinoma (SCC) is one of the most common tumors in the world. Cure for patients with skin SCC is usually achieved by surgical resection of the tumor, which can cause aesthetic and functional changes as tumors appear in exposed areas of the body. Thus, the discovery of new therapies for tumor carriers is of utmost relevance. The researchers in our group produced four complexes containing gold, palladium and silver as potential antitumor agents. The aim of this study was to evaluate the antitumor effects of mercaptothiazoline gold (AuMTZ), triphenylphosphine gold (AuDMAP), deoxylylinine palladium (PdSAC) and nimesulide silver (AgNMS) complexes on skin SCC. The antiproliferative effect of the compounds was evaluated in non-tumoral lineage of immortalized human keratinocytes (HaCaT) and 13 diverse human tumor cell lines, including two tongue SCC4 (SCC4 and SCC15) and one oropharyngeal SCC (FaDu). NCI60 protocol. Due to the higher antiproliferative activities at lower concentrations, AuMTZ and AgNMS were selected to have their efficiencies and safety assessed in the 7,12-dimethylbenzanthracene / 12-o-tetradecanoyl-phorb-13-acetate (DMBA) induced skin model. / TPA) in mice. The animals received bacterial cellulose dressings containing the selected complexes (1 mg / cm2) for 21 days. At the end of the treatment half of the animals were euthanized and the others were clinically followed by 21 additional animals. The body weight of the animals was evaluated every seven days and blood, skin (lesion area) and some internal organs were collected at the end of the experiments. AgNMS reduced the size of tumors without systemic toxicity and regression was maintained after discontinuation of treatment. AuMTZ did not reduce the size of the tumors, did not cause systemic toxicity, but caused burns in animals with intact skin (without tumors), which regressed with treatment interruption. AuMTZ was able to activate caspases in flow cytometry assays. Thus, the application of AgNMS in a cellulose dressing has shown to be quite promising for treating skin SCC but the same cannot be said for AuMTZ in this presentation (AU)

• FAPESP's process: 16/07729-4 - Metal complex from golden, palladium and silver in the treatment of skin squamous cell carcinoma
• Grantee: Tuany Zambroti Cândido
• Support Opportunities: Scholarships in Brazil - Doctorate