Dados do Trabalho

Título

Gallium acetate as a possible chemotherapeutic agent for Triple-Negative Breast Cancer (TNBC) in iron metabolism, DMT1 and transferrin receptor with base in the biochemical model of the Acidithiobacillus ferrooxidans metabolism

Introdução

Triple-Negative Breast Cancer (TNBC) has an important prevalence in the Brazilian population due to its ethnic background, creating enormous challenges in terms of specific therapeutic targets. In this context, the functional importance of iron metabolism in the tumorigenesis process is widely described in the literature, with the exception of cases of TNBC, which do not have published studies on such mechanisms, and due to this peculiarity it becomes a strategy as a pharmacological route.

Objetivo

Aiming the relevance of iron in the processes of proliferation and cell survival in breast tumours, with special focus on the TNBC subtype, the present study uses as a fundamental premise the broad description in the literature on the chemical effects of metal gallium in microbiology and oncology. 

Métodos

For this, basic gallium acetate was synthesised by 3 different routes from the oxide, being characterised by different physical and chemical techniques, since there are no previous records of the same compound in the literature in terms of synthesis and analysis, being unprecedented the process developed. After the characterization, an Elisa plate culture of the extremophile Acidithiobacillus ferrooxidans was set up with the disposition of serial concentrations of the compound (from the control to 15 mM), setting up a survival curve for 7 days of study. In parallel, a culture of normal breast cells (Hs578T) and tumour cells (MCF10A) were previously treated with and without the presence of the compound at an average concentration of 5 mM and obtained similar results with the culture of the bacteria, showing a control in the proliferation and cell survival with metal treatment, with little effect on normal breast cells in culture.

Resultados

Thus, the previous results corroborate the findings already evidenced in the literature in other solid and liquid tumours, such as lymphomas and leukemias, given the inhibitory effect on the proliferation and cell survival not only of bacteria, but also of breast cells in culture, of subtype TNBC. The data collected from the culture growth curves when compared to the control showed a deleterious action of the metal on the biochemistry of both bacteria and breast cells in malignancy, with a small impact on normal breast cells, which in the preliminary results showed a negligible impact on cell proliferation and survival, despite showing repercussions on some cultured cells. In addition, the concentration used in the breast cell experiments followed the results obtained by the bacterium inhibition curve, which presented a control range from 5mM to 9mM, still not well understood in light of the cellular pathways affected in both models.

Conclusões

Therefore, the results obtained in preliminary experiments, both in culture of Acidithiobacillus ferrooxidans and with breast cells, show an enormous therapeutic potential of basic gallium acetate in controlling cell proliferation. Therefore, we have an important highlight as a possible new therapeutic drug, never before synthesised and tested in human breast tumours, requiring further studies and tests on the pharmacological dynamics and real effects of the use of gallium in these models.

Palavras-chave

Gallium, Breast Cancer, Acidithiobacillus ferrooxidans

Financiador do resumo

FAPESP, CAPES, CNPq