Publicação
Anti-tumoral effects of an Iron and a Cobalt Scorpionate
| Resumo: | The World Health Organization (WHO) reports that cancer is the second leading cause of death globally and there have been several research attempts focused on finding more efficient treatments to deal with this disease, including the area of metal-based drugs for cancer chemotherapy. New transition metal complexes are being continuously designed and tested as anticancer agents, namely complexes obtained with the so called scorpionate ligands, which have provided significant contributions in the fields of catalysis and bioinorganic chemistry, and have also shown interesting antitumoral properties. This project was focused on the evaluation of the antiproliferative and antimigration effects of two scorpionate metal complexes as a preliminary approach to assess their anti-tumoral properties. An iron scorpionate, FeCl2Tpm (designated as S6), and a cobalt scorpionate, CoTpm2(OH)2 (termed S7) with tris(pyrazolyl)methane-derived ligands (Tpm), were tested in various representative cell lines, HCT116 (colorectal carcinoma), B16 (murine melanoma) and HaCaT (a non-tumoral line of spontaneously transformed skin keratinocytes), to evaluate their cytotoxic potential towards these cells and their capacity to inhibit cell migration, two features that would provide some insights regarding their anti-tumoral effects. The assessment of the cytotoxicity profile of the compounds S6 and S7 was conducted by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) reduction assays, after confirmation of the purity of the complexes by HPLC (high-performance liquid chromatography). The evaluation of the effects of these scorpionates on cell migration was performed through scratch assays. Samples of cells exposed to S6 and S7 were also prepared and later submitted to metabolomic analyses, that could possibly identify alterations concerning metabolite levels and their respective metabolic pathways. Results revealed that S6 did not exhibit a significant toxicity towards the HCT116 and HaCaT cell lines under the tested conditions, but displayed the capacity to delay cell migration. S6 also led to an increase of the proliferation and migration of the B16 cell line. By contrast, S7 revealed a higher cytotoxic potential in the cell lines used, as well as the capacity to inhibit cell migration. The results obtained with the tested cell lines suggest that S7 could potentially be used as an anti tumoral agent, since this scorpionate complex revealed visible effects in two cellular processes that are particularly enhanced in tumoral cells (proliferation and migration). Further studies are needed to confirm these findings, which could involve testing their role in cell invasion in order to allow a better understanding of the anti-tumoral effects of these scorpionate complexes. |
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| Autores principais: | Silva, Pedro Miguel da Graça |
| Assunto: | Escorpionatos potencial antitumoral efeitos antiproliferativos e antimigratórios Tese de mestrado - 2020 |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | The World Health Organization (WHO) reports that cancer is the second leading cause of death globally and there have been several research attempts focused on finding more efficient treatments to deal with this disease, including the area of metal-based drugs for cancer chemotherapy. New transition metal complexes are being continuously designed and tested as anticancer agents, namely complexes obtained with the so called scorpionate ligands, which have provided significant contributions in the fields of catalysis and bioinorganic chemistry, and have also shown interesting antitumoral properties. This project was focused on the evaluation of the antiproliferative and antimigration effects of two scorpionate metal complexes as a preliminary approach to assess their anti-tumoral properties. An iron scorpionate, FeCl2Tpm (designated as S6), and a cobalt scorpionate, CoTpm2(OH)2 (termed S7) with tris(pyrazolyl)methane-derived ligands (Tpm), were tested in various representative cell lines, HCT116 (colorectal carcinoma), B16 (murine melanoma) and HaCaT (a non-tumoral line of spontaneously transformed skin keratinocytes), to evaluate their cytotoxic potential towards these cells and their capacity to inhibit cell migration, two features that would provide some insights regarding their anti-tumoral effects. The assessment of the cytotoxicity profile of the compounds S6 and S7 was conducted by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) reduction assays, after confirmation of the purity of the complexes by HPLC (high-performance liquid chromatography). The evaluation of the effects of these scorpionates on cell migration was performed through scratch assays. Samples of cells exposed to S6 and S7 were also prepared and later submitted to metabolomic analyses, that could possibly identify alterations concerning metabolite levels and their respective metabolic pathways. Results revealed that S6 did not exhibit a significant toxicity towards the HCT116 and HaCaT cell lines under the tested conditions, but displayed the capacity to delay cell migration. S6 also led to an increase of the proliferation and migration of the B16 cell line. By contrast, S7 revealed a higher cytotoxic potential in the cell lines used, as well as the capacity to inhibit cell migration. The results obtained with the tested cell lines suggest that S7 could potentially be used as an anti tumoral agent, since this scorpionate complex revealed visible effects in two cellular processes that are particularly enhanced in tumoral cells (proliferation and migration). Further studies are needed to confirm these findings, which could involve testing their role in cell invasion in order to allow a better understanding of the anti-tumoral effects of these scorpionate complexes. |
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