(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1

Abstract (–)-Epigallocatechin-3-gallate (EGCG), the major active polyphenol extracted from green tea, has been shown to induce apoptosis and inhibit cell proliferation, cell invasion, angiogenesis and metastasis. Herein, we evaluated the in vivo effects of EGCG in acute myeloid leukaemia (AML) using...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Fernanda Isabel Della Via, Rodrigo Naoto Shiraishi, Irene Santos, Karla Priscila Ferro, Myriam Janeth Salazar-Terreros, Gilberto Carlos Franchi Junior, Eduardo Magalhães Rego, Sara Teresinha Olalla Saad, Cristiane Okuda Torello
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15cd940625e54b17be7e963ebdc0e55b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:15cd940625e54b17be7e963ebdc0e55b
record_format	dspace
spelling	oai:doaj.org-article:15cd940625e54b17be7e963ebdc0e55b2021-12-02T14:53:42Z(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN110.1038/s41598-021-88478-z2045-2322https://doaj.org/article/15cd940625e54b17be7e963ebdc0e55b2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88478-zhttps://doaj.org/toc/2045-2322Abstract (–)-Epigallocatechin-3-gallate (EGCG), the major active polyphenol extracted from green tea, has been shown to induce apoptosis and inhibit cell proliferation, cell invasion, angiogenesis and metastasis. Herein, we evaluated the in vivo effects of EGCG in acute myeloid leukaemia (AML) using an acute promyelocytic leukaemia (APL) experimental model (PML/RARα). Haematological analysis revealed that EGCG treatment reversed leucocytosis, anaemia and thrombocytopenia, and prolonged survival of PML/RARα mice. Notably, EGCG reduced leukaemia immature cells and promyelocytes in the bone marrow while increasing mature myeloid cells, possibly due to apoptosis increase and cell differentiation. The reduction of promyelocytes and neutrophils/monocytes increase detected in the peripheral blood, in addition to the increased percentage of bone marrow cells with aggregated promyelocytic leukaemia (PML) bodies staining and decreased expression of PML-RAR oncoprotein corroborates our results. In addition, EGCG increased expression of neutrophil differentiation markers such as CD11b, CD14, CD15 and CD66 in NB4 cells; and the combination of all-trans retinoic acid (ATRA) plus EGCG yield higher increase the expression of CD15 marker. These findings could be explained by a decrease of peptidyl-prolyl isomerase NIMA-interacting 1 (PIN1) expression and reactive oxygen species (ROS) increase. EGCG also decreased expression of substrate oncoproteins for PIN1 (including cyclin D1, NF-κB p65, c-MYC, and AKT) and 67 kDa laminin receptor (67LR) in the bone marrow cells. Moreover, EGCG showed inhibition of ROS production in NB4 cells in the presence of N-acetyl-L-cysteine (NAC), as well as a partial blockage of neutrophil differentiation and apoptosis, indicating that EGCG-activities involve/or are in response of oxidative stress. Furthermore, apoptosis of spleen cells was supported by increasing expression of BAD and BAX, parallel to BCL-2 and c-MYC decrease. The reduction of spleen weights of PML/RARα mice, as well as apoptosis induced by EGCG in NB4 cells in a dose-dependent manner confirms this assumption. Our results support further evaluation of EGCG in clinical trials for AML, since EGCG could represent a promising option for AML patient ineligible for current mainstay treatments.Fernanda Isabel Della ViaRodrigo Naoto ShiraishiIrene SantosKarla Priscila FerroMyriam Janeth Salazar-TerrerosGilberto Carlos Franchi JuniorEduardo Magalhães RegoSara Teresinha Olalla SaadCristiane Okuda TorelloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fernanda Isabel Della Via Rodrigo Naoto Shiraishi Irene Santos Karla Priscila Ferro Myriam Janeth Salazar-Terreros Gilberto Carlos Franchi Junior Eduardo Magalhães Rego Sara Teresinha Olalla Saad Cristiane Okuda Torello (–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
description	Abstract (–)-Epigallocatechin-3-gallate (EGCG), the major active polyphenol extracted from green tea, has been shown to induce apoptosis and inhibit cell proliferation, cell invasion, angiogenesis and metastasis. Herein, we evaluated the in vivo effects of EGCG in acute myeloid leukaemia (AML) using an acute promyelocytic leukaemia (APL) experimental model (PML/RARα). Haematological analysis revealed that EGCG treatment reversed leucocytosis, anaemia and thrombocytopenia, and prolonged survival of PML/RARα mice. Notably, EGCG reduced leukaemia immature cells and promyelocytes in the bone marrow while increasing mature myeloid cells, possibly due to apoptosis increase and cell differentiation. The reduction of promyelocytes and neutrophils/monocytes increase detected in the peripheral blood, in addition to the increased percentage of bone marrow cells with aggregated promyelocytic leukaemia (PML) bodies staining and decreased expression of PML-RAR oncoprotein corroborates our results. In addition, EGCG increased expression of neutrophil differentiation markers such as CD11b, CD14, CD15 and CD66 in NB4 cells; and the combination of all-trans retinoic acid (ATRA) plus EGCG yield higher increase the expression of CD15 marker. These findings could be explained by a decrease of peptidyl-prolyl isomerase NIMA-interacting 1 (PIN1) expression and reactive oxygen species (ROS) increase. EGCG also decreased expression of substrate oncoproteins for PIN1 (including cyclin D1, NF-κB p65, c-MYC, and AKT) and 67 kDa laminin receptor (67LR) in the bone marrow cells. Moreover, EGCG showed inhibition of ROS production in NB4 cells in the presence of N-acetyl-L-cysteine (NAC), as well as a partial blockage of neutrophil differentiation and apoptosis, indicating that EGCG-activities involve/or are in response of oxidative stress. Furthermore, apoptosis of spleen cells was supported by increasing expression of BAD and BAX, parallel to BCL-2 and c-MYC decrease. The reduction of spleen weights of PML/RARα mice, as well as apoptosis induced by EGCG in NB4 cells in a dose-dependent manner confirms this assumption. Our results support further evaluation of EGCG in clinical trials for AML, since EGCG could represent a promising option for AML patient ineligible for current mainstay treatments.
format	article
author	Fernanda Isabel Della Via Rodrigo Naoto Shiraishi Irene Santos Karla Priscila Ferro Myriam Janeth Salazar-Terreros Gilberto Carlos Franchi Junior Eduardo Magalhães Rego Sara Teresinha Olalla Saad Cristiane Okuda Torello
author_facet	Fernanda Isabel Della Via Rodrigo Naoto Shiraishi Irene Santos Karla Priscila Ferro Myriam Janeth Salazar-Terreros Gilberto Carlos Franchi Junior Eduardo Magalhães Rego Sara Teresinha Olalla Saad Cristiane Okuda Torello
author_sort	Fernanda Isabel Della Via
title	(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
title_short	(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
title_full	(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
title_fullStr	(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
title_full_unstemmed	(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
title_sort	(–)-epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and pin1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/15cd940625e54b17be7e963ebdc0e55b
work_keys_str_mv	AT fernandaisabeldellavia epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT rodrigonaotoshiraishi epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT irenesantos epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT karlapriscilaferro epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT myriamjanethsalazarterreros epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT gilbertocarlosfranchijunior epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT eduardomagalhaesrego epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT sarateresinhaolallasaad epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1 AT cristianeokudatorello epigallocatechin3gallateinducesapoptosisanddifferentiationinleukaemiabytargetingreactiveoxygenspeciesandpin1
_version_	1718389368371019776

(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1

Ejemplares similares