Cargando…

Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo

Loss of endoplasmic reticulum (ER) homeostasis leads to ER stress, thus prolonged activation can lead to apoptosis. Herein, artesunate (ART) induced ER stress in leukaemia cells, resulting in eIF2α phosphorylation, activation of transcription factor 4, subsequent CHOP upregulation and XBP1 splicing....

Descripción completa

Detalles Bibliográficos
Autores principales: Mancuso, Rubia Isler, Azambuja, Juliana Hofstätter, Niemann, Fernanda Soares, Congrains, Ada, Foglio, Mary Ann, Rego, Eduardo Magalhães, Olalla Saad, Sara Teresinha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175883/
https://www.ncbi.nlm.nih.gov/pubmed/35845184
http://dx.doi.org/10.1002/jha2.314
_version_ 1784722543141191680
author Mancuso, Rubia Isler
Azambuja, Juliana Hofstätter
Niemann, Fernanda Soares
Congrains, Ada
Foglio, Mary Ann
Rego, Eduardo Magalhães
Olalla Saad, Sara Teresinha
author_facet Mancuso, Rubia Isler
Azambuja, Juliana Hofstätter
Niemann, Fernanda Soares
Congrains, Ada
Foglio, Mary Ann
Rego, Eduardo Magalhães
Olalla Saad, Sara Teresinha
author_sort Mancuso, Rubia Isler
collection PubMed
description Loss of endoplasmic reticulum (ER) homeostasis leads to ER stress, thus prolonged activation can lead to apoptosis. Herein, artesunate (ART) induced ER stress in leukaemia cells, resulting in eIF2α phosphorylation, activation of transcription factor 4, subsequent CHOP upregulation and XBP1 splicing. Furthermore, in vitro cyclin/CDKs reduction induced G1‐phase arrest. An in vivo xenograft model showed a consistent pattern of ART in reducing tumour burden, supporting roles in the UPR pathway, which we speculate could lead to apoptosis by NOXA activation. Moreover, ART were capable of increasing the survival of mice. Taken together, our data indicate that ART may represent an interesting weapon to fight leukaemia.
format Online
Article
Text
id pubmed-9175883
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-91758832022-07-14 Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo Mancuso, Rubia Isler Azambuja, Juliana Hofstätter Niemann, Fernanda Soares Congrains, Ada Foglio, Mary Ann Rego, Eduardo Magalhães Olalla Saad, Sara Teresinha EJHaem Short Reports Loss of endoplasmic reticulum (ER) homeostasis leads to ER stress, thus prolonged activation can lead to apoptosis. Herein, artesunate (ART) induced ER stress in leukaemia cells, resulting in eIF2α phosphorylation, activation of transcription factor 4, subsequent CHOP upregulation and XBP1 splicing. Furthermore, in vitro cyclin/CDKs reduction induced G1‐phase arrest. An in vivo xenograft model showed a consistent pattern of ART in reducing tumour burden, supporting roles in the UPR pathway, which we speculate could lead to apoptosis by NOXA activation. Moreover, ART were capable of increasing the survival of mice. Taken together, our data indicate that ART may represent an interesting weapon to fight leukaemia. John Wiley and Sons Inc. 2021-10-16 /pmc/articles/PMC9175883/ /pubmed/35845184 http://dx.doi.org/10.1002/jha2.314 Text en © 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Reports
Mancuso, Rubia Isler
Azambuja, Juliana Hofstätter
Niemann, Fernanda Soares
Congrains, Ada
Foglio, Mary Ann
Rego, Eduardo Magalhães
Olalla Saad, Sara Teresinha
Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
title Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
title_full Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
title_fullStr Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
title_full_unstemmed Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
title_short Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
title_sort artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
topic Short Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175883/
https://www.ncbi.nlm.nih.gov/pubmed/35845184
http://dx.doi.org/10.1002/jha2.314
work_keys_str_mv AT mancusorubiaisler artemisininsinduceendoplasmicreticulumstressinacuteleukaemiacellsinvitroandinvivo
AT azambujajulianahofstatter artemisininsinduceendoplasmicreticulumstressinacuteleukaemiacellsinvitroandinvivo
AT niemannfernandasoares artemisininsinduceendoplasmicreticulumstressinacuteleukaemiacellsinvitroandinvivo
AT congrainsada artemisininsinduceendoplasmicreticulumstressinacuteleukaemiacellsinvitroandinvivo
AT fogliomaryann artemisininsinduceendoplasmicreticulumstressinacuteleukaemiacellsinvitroandinvivo
AT regoeduardomagalhaes artemisininsinduceendoplasmicreticulumstressinacuteleukaemiacellsinvitroandinvivo
AT olallasaadsarateresinha artemisininsinduceendoplasmicreticulumstressinacuteleukaemiacellsinvitroandinvivo