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

Autor: Irene Santos, Sara Teresinha Olalla Saad, Rodrigo Naoto Shiraishi, Fernanda I Della Via, Eduardo Magalhães Rego, Gilberto Carlos Franchi Junior, Karla Priscila Ferro, Cristiane Okuda Torello, Myriam Salazar-Terreros
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Science
Cellular differentiation
Apoptosis
Mice
Transgenic
medicine.disease_cause
complex mixtures
Catechin
Article
Acute myeloid leukaemia
03 medical and health sciences
0302 clinical medicine
Leukemia
Promyelocytic
Acute
Neutrophil differentiation
medicine
Animals
Humans
Cancer models
Protein kinase B
bcl-2-Associated X Protein
chemistry.chemical_classification
Reactive oxygen species
Leukemia
Experimental
Multidisciplinary
Cell growth
Retinoic Acid Receptor alpha
food and beverages
Cell Differentiation
Antineoplastic Agents
Phytogenic
NIMA-Interacting Peptidylprolyl Isomerase
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Cancer research
Medicine
bcl-Associated Death Protein
Bone marrow
Reactive Oxygen Species
Spleen
Oxidative stress
Zdroj: Scientific Reports
Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
ISSN: 2045-2322
Popis: (–)-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.
Databáze: OpenAIRE
Externí odkaz: