Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases
- Autores
- Martínez, Valeria Romina; Aguirre, María Victoria; Todaro, Juan Santiago; Piro, Oscar Enrique; Echeverría, Gustavo Alberto; Naso, Luciana Gissella; Ferrer, Evelina Gloria; Williams, Patricia Ana María
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- A new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was synthesized and characterized. The crystal structure was determined by x-ray diffraction methods. When aqueous solutions of the ligand and the metal were mixed, the known and more soluble powder [Zn(Los)₂].3H₂O (ZnLos) complex has been obtained. The interactions with phosphatases showed a concerted mechanism displayed by the Zn ions and ZnLos up to 500 μM concentration: a decrease of the acid phosphatase (AcP) associated with an increase in the alkaline phosphatase (ALP) activities. The complex and ZnSO₄ showed a cytotoxic behavior on human lung A549 cancer cell line at concentrations higher than 75 μM with reactive oxygen species (ROS) generation and GSH (and GSH/GSSG ratio) depletion. Apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method, a mechanism accompanied by upregulation of BAX protein, downregulation of Bcl-XL and release of caspase-3. The BAX/Bcl-XL ratio was found to be significantly higher in cells exposure to ZnLos than cells treated with ZnSO₄, in agreement with the higher apoptotic percentage of cells found for the complex. Cell death was found to be produced by apoptosis and no necrosis has been observed. On the contrary, losartan exerted low effects on phosphatases, produced some reduction of cancer cell viability (concentrations > 250 μM, number of apoptotic cells similar to the basal) with low ROS depletion, without alteration of the GSH/GSSG and low BAX/Bcl-XL ratios. In the MRC-5, normal lung fibroblasts cell line only ZnSO₄ at concentrations higher than 200 μM displays cytotoxic effects.
Centro de Química Inorgánica
Instituto de Física La Plata - Materia
-
Ciencias Exactas
Química
Losartan
Zinc coordination
Enzymatic inhibition
Anticancer mechanism - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by/4.0/
- Repositorio
.jpg)
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/145282
Ver los metadatos del registro completo
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Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid PhosphatasesMartínez, Valeria RominaAguirre, María VictoriaTodaro, Juan SantiagoPiro, Oscar EnriqueEcheverría, Gustavo AlbertoNaso, Luciana GissellaFerrer, Evelina GloriaWilliams, Patricia Ana MaríaCiencias ExactasQuímicaLosartanZinc coordinationEnzymatic inhibitionAnticancer mechanismA new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was synthesized and characterized. The crystal structure was determined by x-ray diffraction methods. When aqueous solutions of the ligand and the metal were mixed, the known and more soluble powder [Zn(Los)₂].3H₂O (ZnLos) complex has been obtained. The interactions with phosphatases showed a concerted mechanism displayed by the Zn ions and ZnLos up to 500 μM concentration: a decrease of the acid phosphatase (AcP) associated with an increase in the alkaline phosphatase (ALP) activities. The complex and ZnSO₄ showed a cytotoxic behavior on human lung A549 cancer cell line at concentrations higher than 75 μM with reactive oxygen species (ROS) generation and GSH (and GSH/GSSG ratio) depletion. Apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method, a mechanism accompanied by upregulation of BAX protein, downregulation of Bcl-XL and release of caspase-3. The BAX/Bcl-XL ratio was found to be significantly higher in cells exposure to ZnLos than cells treated with ZnSO₄, in agreement with the higher apoptotic percentage of cells found for the complex. Cell death was found to be produced by apoptosis and no necrosis has been observed. On the contrary, losartan exerted low effects on phosphatases, produced some reduction of cancer cell viability (concentrations > 250 μM, number of apoptotic cells similar to the basal) with low ROS depletion, without alteration of the GSH/GSSG and low BAX/Bcl-XL ratios. In the MRC-5, normal lung fibroblasts cell line only ZnSO₄ at concentrations higher than 200 μM displays cytotoxic effects.Centro de Química InorgánicaInstituto de Física La Plata2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf413-429http://sedici.unlp.edu.ar/handle/10915/145282enginfo:eu-repo/semantics/altIdentifier/issn/1559-0720info:eu-repo/semantics/altIdentifier/issn/0163-4984info:eu-repo/semantics/altIdentifier/doi/10.1007/s12011-018-1334-xinfo:eu-repo/semantics/altIdentifier/pmid/29651733info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-15T11:24:09Zoai:sedici.unlp.edu.ar:10915/145282Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-15 11:24:09.878SEDICI (UNLP) - Universidad Nacional de La Platafalse |
| dc.title.none.fl_str_mv |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases |
| title |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases |
| spellingShingle |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases Martínez, Valeria Romina Ciencias Exactas Química Losartan Zinc coordination Enzymatic inhibition Anticancer mechanism |
| title_short |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases |
| title_full |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases |
| title_fullStr |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases |
| title_full_unstemmed |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases |
| title_sort |
Interaction of Zn with Losartan : Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases |
| dc.creator.none.fl_str_mv |
Martínez, Valeria Romina Aguirre, María Victoria Todaro, Juan Santiago Piro, Oscar Enrique Echeverría, Gustavo Alberto Naso, Luciana Gissella Ferrer, Evelina Gloria Williams, Patricia Ana María |
| author |
Martínez, Valeria Romina |
| author_facet |
Martínez, Valeria Romina Aguirre, María Victoria Todaro, Juan Santiago Piro, Oscar Enrique Echeverría, Gustavo Alberto Naso, Luciana Gissella Ferrer, Evelina Gloria Williams, Patricia Ana María |
| author_role |
author |
| author2 |
Aguirre, María Victoria Todaro, Juan Santiago Piro, Oscar Enrique Echeverría, Gustavo Alberto Naso, Luciana Gissella Ferrer, Evelina Gloria Williams, Patricia Ana María |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Ciencias Exactas Química Losartan Zinc coordination Enzymatic inhibition Anticancer mechanism |
| topic |
Ciencias Exactas Química Losartan Zinc coordination Enzymatic inhibition Anticancer mechanism |
| dc.description.none.fl_txt_mv |
A new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was synthesized and characterized. The crystal structure was determined by x-ray diffraction methods. When aqueous solutions of the ligand and the metal were mixed, the known and more soluble powder [Zn(Los)₂].3H₂O (ZnLos) complex has been obtained. The interactions with phosphatases showed a concerted mechanism displayed by the Zn ions and ZnLos up to 500 μM concentration: a decrease of the acid phosphatase (AcP) associated with an increase in the alkaline phosphatase (ALP) activities. The complex and ZnSO₄ showed a cytotoxic behavior on human lung A549 cancer cell line at concentrations higher than 75 μM with reactive oxygen species (ROS) generation and GSH (and GSH/GSSG ratio) depletion. Apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method, a mechanism accompanied by upregulation of BAX protein, downregulation of Bcl-XL and release of caspase-3. The BAX/Bcl-XL ratio was found to be significantly higher in cells exposure to ZnLos than cells treated with ZnSO₄, in agreement with the higher apoptotic percentage of cells found for the complex. Cell death was found to be produced by apoptosis and no necrosis has been observed. On the contrary, losartan exerted low effects on phosphatases, produced some reduction of cancer cell viability (concentrations > 250 μM, number of apoptotic cells similar to the basal) with low ROS depletion, without alteration of the GSH/GSSG and low BAX/Bcl-XL ratios. In the MRC-5, normal lung fibroblasts cell line only ZnSO₄ at concentrations higher than 200 μM displays cytotoxic effects. Centro de Química Inorgánica Instituto de Física La Plata |
| description |
A new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was synthesized and characterized. The crystal structure was determined by x-ray diffraction methods. When aqueous solutions of the ligand and the metal were mixed, the known and more soluble powder [Zn(Los)₂].3H₂O (ZnLos) complex has been obtained. The interactions with phosphatases showed a concerted mechanism displayed by the Zn ions and ZnLos up to 500 μM concentration: a decrease of the acid phosphatase (AcP) associated with an increase in the alkaline phosphatase (ALP) activities. The complex and ZnSO₄ showed a cytotoxic behavior on human lung A549 cancer cell line at concentrations higher than 75 μM with reactive oxygen species (ROS) generation and GSH (and GSH/GSSG ratio) depletion. Apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method, a mechanism accompanied by upregulation of BAX protein, downregulation of Bcl-XL and release of caspase-3. The BAX/Bcl-XL ratio was found to be significantly higher in cells exposure to ZnLos than cells treated with ZnSO₄, in agreement with the higher apoptotic percentage of cells found for the complex. Cell death was found to be produced by apoptosis and no necrosis has been observed. On the contrary, losartan exerted low effects on phosphatases, produced some reduction of cancer cell viability (concentrations > 250 μM, number of apoptotic cells similar to the basal) with low ROS depletion, without alteration of the GSH/GSSG and low BAX/Bcl-XL ratios. In the MRC-5, normal lung fibroblasts cell line only ZnSO₄ at concentrations higher than 200 μM displays cytotoxic effects. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-12 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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http://sedici.unlp.edu.ar/handle/10915/145282 |
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eng |
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eng |
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openAccess |
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http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) |
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application/pdf 413-429 |
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