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

Rubia Isler Mancuso; Juliana Hofstätter Azambuja; Fernanda Soares Niemann; Ada Congrains; Mary Ann Foglio; Eduardo Magalhães Rego; Sara Teresinha Olalla Saad

doi:10.1002/jha2.314

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

EJHaem. 2021 Oct 16;2(4):818-822. doi: 10.1002/jha2.314. eCollection 2021 Nov.

Authors

Rubia Isler Mancuso¹, Juliana Hofstätter Azambuja¹, Fernanda Soares Niemann¹, Ada Congrains¹, Mary Ann Foglio², Eduardo Magalhães Rego^{3

4}, Sara Teresinha Olalla Saad¹

Affiliations

¹ Haematology and Transfusion Medicine Center University of Campinas Campinas Brazil.
² Faculty of Pharmaceutical Science University of Campinas Campinas Brazil.
³ Center for Cell Based Therapy University of São Paulo Ribeirão Preto Brazil.
⁴ Haematology Division, LIM31, Faculdade de Medicina University of São Paulo São Paulo Brazil.

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.

Keywords: acute leukaemia; artemisinin; artesunate; endoplasmic reticulum stress.