Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells
Overheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach...
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MDPI AG
2021-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/12/1848 |
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| author | Javier Quero Francesco Ruighi Jesús Osada M. Concepción Gimeno Elena Cerrada Maria Jesús Rodriguez-Yoldi |
| author_facet | Javier Quero Francesco Ruighi Jesús Osada M. Concepción Gimeno Elena Cerrada Maria Jesús Rodriguez-Yoldi |
| author_sort | Javier Quero |
| collection | DOAJ |
| description | Overheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules is the incorporation of fluorine atoms in the chemical structure, since fluor can tune some chemical properties such as binding affinity. Herein we report the anticancer effect of gold derivatives with phosphanes derived from 1,3,5-triaza-7-phosphaadamantane (PTA) with long hydrocarbon chains and the homologous fluorinated chains. Besides, we analysed the influence of temperature in the cytotoxic effect. The studied gold(I) complexes with phosphanes derived from PTA showed antiproliferative effect on human colon carcinoma cells (Caco-2/TC7 cell line), probably by inhibiting cellular TrxR causing a dysfunction in the intracellular redox state. In addition, the cell cycle was altered by the activation of p53, and the complexes produce apoptosis through mitochondrial depolarization and the consequent activation of caspase-3. Furthermore, the results suggest that this cytotoxic effect is enhanced by hyperthermia and the presence of polyfluorinated chains. |
| first_indexed | 2024-03-10T04:34:11Z |
| format | Article |
| id | doaj.art-db9a1ec78a704aea8aded09e4775fa8f |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T04:34:11Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-db9a1ec78a704aea8aded09e4775fa8f2023-11-23T03:56:31ZengMDPI AGBiomedicines2227-90592021-12-01912184810.3390/biomedicines9121848Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon CellsJavier Quero0Francesco Ruighi1Jesús Osada2M. Concepción Gimeno3Elena Cerrada4Maria Jesús Rodriguez-Yoldi5Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, SpainDepartamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, SpainCIBERobn, IIS Aragón, IA2, Departamento de Bioquímica y Biología Molecular, Unidad de Bioquímica, Universidad de Zaragoza, 50013 Zaragoza, SpainDepartamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, SpainDepartamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, SpainCIBERobn, IIS Aragón, IA2, Departamento de Farmacología y Fisiología y Medicina Legal y Forense, Unidad de Fisiología, Universidad de Zaragoza, 50013 Zaragoza, SpainOverheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules is the incorporation of fluorine atoms in the chemical structure, since fluor can tune some chemical properties such as binding affinity. Herein we report the anticancer effect of gold derivatives with phosphanes derived from 1,3,5-triaza-7-phosphaadamantane (PTA) with long hydrocarbon chains and the homologous fluorinated chains. Besides, we analysed the influence of temperature in the cytotoxic effect. The studied gold(I) complexes with phosphanes derived from PTA showed antiproliferative effect on human colon carcinoma cells (Caco-2/TC7 cell line), probably by inhibiting cellular TrxR causing a dysfunction in the intracellular redox state. In addition, the cell cycle was altered by the activation of p53, and the complexes produce apoptosis through mitochondrial depolarization and the consequent activation of caspase-3. Furthermore, the results suggest that this cytotoxic effect is enhanced by hyperthermia and the presence of polyfluorinated chains.https://www.mdpi.com/2227-9059/9/12/1848hyperthermiaPTAgoldthiolatecolon cancerTrxR |
| spellingShingle | Javier Quero Francesco Ruighi Jesús Osada M. Concepción Gimeno Elena Cerrada Maria Jesús Rodriguez-Yoldi Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells Biomedicines hyperthermia PTA gold thiolate colon cancer TrxR |
| title | Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells |
| title_full | Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells |
| title_fullStr | Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells |
| title_full_unstemmed | Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells |
| title_short | Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells |
| title_sort | gold i complexes bearing alkylated 1 3 5 triaza 7 phosphaadamantane ligands as thermoresponsive anticancer agents in human colon cells |
| topic | hyperthermia PTA gold thiolate colon cancer TrxR |
| url | https://www.mdpi.com/2227-9059/9/12/1848 |
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