Dados do Trabalho

Título

Evaluation in vitro of the gold(I) complex with triphenylphosphine and 4-dimethylaaminepyridine as ligands in skin cancer

Introdução/Justificativa

Closely related to high UV exposure and comprising basal cell carcinoma, squamous cell carcinoma (SCC), and melanoma, skin cancer is the most prevalent tumor in the world. Cisplatin has been used for treatment of patients with skin squamous cell carcinoma (SSCC) with low response rate and pronounced adverse effects. Thus, the search for new chemotherapeutic agents for patients with SSCC or melanoma is required, and gold complexes have been explored as potential anticancer drugs. Targeting thioredoxin reductase or thiol-rich proteins, many gold complexes can induce cell death by reactive oxygen species.

Objetivos

Our study aimed to evaluate the in vitro anti-proliferative effects of a gold(I) complex with triphenylphosphine and 4-dimethylaminopyridine as ligand.

Materiais e Métodos

The gold (I) complex was synthesized at the Department of Inorganic Chemistry, Institute of Chemistry, University of Campinas. Melanoma (UACC-62), squamous cell carcinoma of tongue (SCC4 and SCC15), and a non-tumoral cell line (HaCat, immortalized keratinocyte) were grown in complete medium [RPMI-1640 (Gilco®) supplemented with 5% fetal bovine serum (Gilco®) and 1% penicillin:streptomycin mixture (1000 U/mL:1000 µg/mL, Vitrocell, Brasil)] at 37 °C and 5% CO2. Each cell line (100 μL/well, in 96-well plates, 4 - 6 x10^4 cel/ml) was exposed to the gold (I) complex (100 μL/well, 0.25 to 250 µg/mL, in triplicate) and incubated for 48 h. Doxorubicin (100 μL/well, 0.025 to 25 µg/mL, in triplicate) was used as a positive control. Before (T0) and after (T1) sample addition, cells were fixed with 50% trichloroacetic acid (TCA, 50 μL/well), and cell viability was determined using the sulforhodamine B protocol at 540 nm with a microplate reader spectrophotometer (VersaMax, Molecular Devices). The difference between T0 and T1 absorbance values represented 100% of cell growth, and the proliferation (%) of each cell line in the presence of each sample concentration was calculated accordingly. Effective
concentration representing the sample concentration required to promote 50% growth inhibition (GI50) for each cell line was calculated by sigmoidal regression using Origin 8.0 software.

Resultados

The gold(I) complex showed potent anti-proliferative effect against UACC-62 cells (GI50 < 0.25 µg mL-1) being less active against SCC15 (GI50 ≈ 2.5 µg mL-1) and SCC4 (GI50: 10.2 µg mL-1) cells. Moreover, the anti-proliferative effect of gold(I) complex showed a good selectivity being almost 10x less active against HaCaT cells (GI50 ≈ 2.5 µg mL-1) in comparison to melanoma cells.

Conclusão

This data indicated gold(I) complex with triphenylphosphine and 4-dimethylaminopyridine as ligands as a promisor candidate for treatment of patients with melanoma. Further in vitro and in vivo evaluations is required to evaluate the mechanism of action and toxicity of the complex. Acknowledgements: The study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio ao Ensino e à Pesquisa do Estado de São Paulo (FAPESP #2016/07729-4; #2023/09738-4; Cancer Theranostics Innovation Center,
(CancerThera), CEPID FAPESP #2021/10265-8), and International Atomic Energy Agency (IAEA) technical cooperation projects for development of Latin American Countries (IAEA/TCLAC: EX-BRA6033-2401375).

Palavras Chave

gold(I) complex; SSCC; melanoma; antiproliferative effect;

Área

Oncologia Pré-Clínica