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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 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.

SUBMITTER: Mancuso RI

PROVIDER: S-EPMC9175883 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

Mancuso Rubia Isler RI Azambuja Juliana Hofstätter JH Niemann Fernanda Soares FS Congrains Ada A Foglio Mary Ann MA Rego Eduardo Magalhães EM Olalla Saad Sara Teresinha ST

EJHaem 20211016 4

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, whic ...[more]

PMID: 35845184

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