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

eJHaem

article

Rubia Isler Mancuso¹  Juliana Hofstätter Azambuja¹  Fernanda Soares Niemann¹  Ada Congrains¹  Mary Ann Foglio²  Eduardo Magalhães Rego³  Sara Teresinha Olalla Saad¹ 

[1] Haematology and Transfusion Medicine Center, University of Campinas;Faculty of Pharmaceutical Science, University of Campinas;Center for Cell Based Therapy, University of São Paulo;Haematology Division, LIM31, Faculdade de Medicina, University of São Paulo

关键词: acute leukaemia;    artemisinin;    artesunate;    endoplasmic reticulum stress;   

DOI  :  10.1002/jha2.314

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown