Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells

Abstract: Thyroid hormones (THs) - 3,3',5-triiodo-L-thyronine (T3) and L-thyroxine (T4) - are important regulators of the metabolism and physiology of most normal tissues. Cytochrome P450 family 3A members are drug metabolizing enzymes involved in the activation and detoxification of several dr...

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Autores principales: Díaz Flaqué, María Celeste, Cayrol, María Florencia, Sterle, Helena Andrea, Aschero, María del Rosario, Díaz Albuja, Johanna Abigail, Isse, Blanca, Farías, Ricardo Norberto, Cerchietti, Leandro, Rosemblit, Cinthia, Cremaschi, Graciela Alicia
Formato: Artículo
Lenguaje:Inglés
Publicado: Impact Journals 2019
Materias:
GLANDULA TIROIDES
HORMONAS
METABOLISMO
QUIMIOTERAPIA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8674
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8674
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic GLANDULA TIROIDES
HORMONAS
METABOLISMO
QUIMIOTERAPIA
spellingShingle GLANDULA TIROIDES
HORMONAS
METABOLISMO
QUIMIOTERAPIA
Díaz Flaqué, María Celeste
Cayrol, María Florencia
Sterle, Helena Andrea
Aschero, María del Rosario
Díaz Albuja, Johanna Abigail
Isse, Blanca
Farías, Ricardo Norberto
Cerchietti, Leandro
Rosemblit, Cinthia
Cremaschi, Graciela Alicia
Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells
topic_facet GLANDULA TIROIDES
HORMONAS
METABOLISMO
QUIMIOTERAPIA
description Abstract: Thyroid hormones (THs) - 3,3',5-triiodo-L-thyronine (T3) and L-thyroxine (T4) - are important regulators of the metabolism and physiology of most normal tissues. Cytochrome P450 family 3A members are drug metabolizing enzymes involved in the activation and detoxification of several drugs. CYP3A4 is the major enzyme involved in the metabolism of chemotherapeutic drugs. In this work, we demonstrate that THs induce a significant increase in CYP3A4 mRNA levels, protein expression and metabolic activity through the membrane receptor integrin αvβ3 and the activation of signalling pathways through Stat1 and NF-κB. We reasoned that TH-induced CYP3A4 modulation may act as an important regulator in the metabolism of doxorubicin (Doxo). Experiments in vitro demonstrated that in CYP3A4-knocked down cells, no TH-mediated chemosensitivity to Doxo was observed. We also found that THs modulate these functions by activating the membrane receptor integrin αvβ3. In addition, we showed that the thyroid status can modulate CYP450 mRNA levels in tumor and liver tissues, and the tumor volume in response to chemotherapy in vivo. In fact, Doxo treatment in hypothyroid mice was associated with lower tumors, displaying lower levels of CYP enzymes, than euthyroid mice. However, higher mRNA levels of CYP enzymes were found in livers from Doxo treated hypothyroid mice respect to control. These results present a new mechanism by which TH could modulate chemotherapy response. These findings highlight the importance of evaluating thyroid status in patients during application of T-cell lymphoma therapeutic regimens.
format Artículo
author Díaz Flaqué, María Celeste
Cayrol, María Florencia
Sterle, Helena Andrea
Aschero, María del Rosario
Díaz Albuja, Johanna Abigail
Isse, Blanca
Farías, Ricardo Norberto
Cerchietti, Leandro
Rosemblit, Cinthia
Cremaschi, Graciela Alicia
author_facet Díaz Flaqué, María Celeste
Cayrol, María Florencia
Sterle, Helena Andrea
Aschero, María del Rosario
Díaz Albuja, Johanna Abigail
Isse, Blanca
Farías, Ricardo Norberto
Cerchietti, Leandro
Rosemblit, Cinthia
Cremaschi, Graciela Alicia
author_sort Díaz Flaqué, María Celeste
title Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells
title_short Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells
title_full Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells
title_fullStr Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells
title_full_unstemmed Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells
title_sort thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma t cells
publisher Impact Journals
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8674
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