Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo
Abstract 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-11-01
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| Series: | eJHaem |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jha2.314 |
| _version_ | 1797740089698156544 |
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| author | Rubia Isler Mancuso Juliana Hofstätter Azambuja Fernanda Soares Niemann Ada Congrains Mary Ann Foglio Eduardo Magalhães Rego Sara Teresinha Olalla Saad |
| author_facet | Rubia Isler Mancuso Juliana Hofstätter Azambuja Fernanda Soares Niemann Ada Congrains Mary Ann Foglio Eduardo Magalhães Rego Sara Teresinha Olalla Saad |
| author_sort | Rubia Isler Mancuso |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T14:07:31Z |
| format | Article |
| id | doaj.art-3888e08a0ce64834bc977e962c16f173 |
| institution | Directory Open Access Journal |
| issn | 2688-6146 |
| language | English |
| last_indexed | 2024-03-12T14:07:31Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | eJHaem |
| spelling | doaj.art-3888e08a0ce64834bc977e962c16f1732023-08-21T14:05:23ZengWileyeJHaem2688-61462021-11-012481882210.1002/jha2.314Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivoRubia Isler Mancuso0Juliana Hofstätter Azambuja1Fernanda Soares Niemann2Ada Congrains3Mary Ann Foglio4Eduardo Magalhães Rego5Sara Teresinha Olalla Saad6Haematology and Transfusion Medicine Center University of Campinas Campinas BrazilHaematology and Transfusion Medicine Center University of Campinas Campinas BrazilHaematology and Transfusion Medicine Center University of Campinas Campinas BrazilHaematology and Transfusion Medicine Center University of Campinas Campinas BrazilFaculty of Pharmaceutical Science University of Campinas Campinas BrazilCenter for Cell Based Therapy University of São Paulo Ribeirão Preto BrazilHaematology and Transfusion Medicine Center University of Campinas Campinas BrazilAbstract 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.https://doi.org/10.1002/jha2.314acute leukaemiaartemisininartesunateendoplasmic reticulum stress |
| spellingShingle | Rubia Isler Mancuso Juliana Hofstätter Azambuja Fernanda Soares Niemann Ada Congrains Mary Ann Foglio Eduardo Magalhães Rego Sara Teresinha Olalla Saad Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo eJHaem acute leukaemia artemisinin artesunate endoplasmic reticulum stress |
| 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 | acute leukaemia artemisinin artesunate endoplasmic reticulum stress |
| url | https://doi.org/10.1002/jha2.314 |
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