Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2355 |
Resumo: | Carbidopa is used for the treatment of Parkinson's disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa. |
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Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative MetaboliteA375 cell line; MCF-7 cell linecarbidopaindole-3-acetonitriletryptophanCarbidopa is used for the treatment of Parkinson's disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT, in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).” NV thanks FCT for IF position, Fundação Manuel António da Mota (FMAM, Portugal) for support. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the FCT and FMAMMDPIRepositório Científico do Centro Hospitalar Universitário de Santo AntónioDuarte, D.Amaro, F.Silva, I.Silva, D.Fresco, P.Oliveira, José CarlosREGUENGO, HENRIQUEGonçalves, J.Vale, N.2020-04-16T15:15:11Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2355engDuarte D, Amaro F, Silva I, et al. Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite. Biomolecules. 2019;9(9):409. Published 2019 Aug 24. doi:10.3390/biom90904092218-273X10.3390/biom9090409info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T11:00:27Zoai:repositorio.chporto.pt:10400.16/2355Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:33.858034Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite |
title |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite |
spellingShingle |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite Duarte, D. A375 cell line; MCF-7 cell line carbidopa indole-3-acetonitrile tryptophan |
title_short |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite |
title_full |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite |
title_fullStr |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite |
title_full_unstemmed |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite |
title_sort |
Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite |
author |
Duarte, D. |
author_facet |
Duarte, D. Amaro, F. Silva, I. Silva, D. Fresco, P. Oliveira, José Carlos REGUENGO, HENRIQUE Gonçalves, J. Vale, N. |
author_role |
author |
author2 |
Amaro, F. Silva, I. Silva, D. Fresco, P. Oliveira, José Carlos REGUENGO, HENRIQUE Gonçalves, J. Vale, N. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Duarte, D. Amaro, F. Silva, I. Silva, D. Fresco, P. Oliveira, José Carlos REGUENGO, HENRIQUE Gonçalves, J. Vale, N. |
dc.subject.por.fl_str_mv |
A375 cell line; MCF-7 cell line carbidopa indole-3-acetonitrile tryptophan |
topic |
A375 cell line; MCF-7 cell line carbidopa indole-3-acetonitrile tryptophan |
description |
Carbidopa is used for the treatment of Parkinson's disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z 2020-04-16T15:15:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2355 |
url |
http://hdl.handle.net/10400.16/2355 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Duarte D, Amaro F, Silva I, et al. Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite. Biomolecules. 2019;9(9):409. Published 2019 Aug 24. doi:10.3390/biom9090409 2218-273X 10.3390/biom9090409 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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MDPI |
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MDPI |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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