Artemisinins induce endoplasmic reticulum stress in acute leukaemia cells in vitro and in vivo.
Rubia Isler MancusoJuliana Hofstätter AzambujaFernanda Soares NiemannAda CongrainsMary Ann FoglioEduardo Magalhães RegoSara Teresinha Olalla SaadPublished in: EJHaem (2021)
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.
Keyphrases
- endoplasmic reticulum stress
- induced apoptosis
- cell cycle arrest
- endoplasmic reticulum
- cell death
- oxidative stress
- hiv infected
- pi k akt
- diabetic rats
- transcription factor
- signaling pathway
- high glucose
- antiretroviral therapy
- drug induced
- cell cycle
- liver failure
- cell proliferation
- intensive care unit
- endothelial cells
- diffuse large b cell lymphoma
- type diabetes
- electronic health record
- risk factors
- artificial intelligence
- extracorporeal membrane oxygenation
- machine learning
- free survival
- genome wide identification