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Induction of autophagy and autophagy-dependent apoptosis in diffuse large B-cell lymphoma by a new antimalarial artemisinin derivative, SM1044

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  • Additional Information
    • Contributors:
      Shanghai Institute of Hematology; Shanghai Jiao Tong University School of Medicine-Shanghai Rui Jin Hospital; First Affiliated Hospital of Nanjing Medical University; Service d'hématolgie adulte; Université Paris Descartes - Paris 5 (UPD5)-Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB); Établissement Français du Sang Auvergne-Rhône-Alpes Lyon (EFS Auvergne-Rhône-Alpes - Lyon); Établissement Français du Sang La Plaine Saint-Denis (EFS)-Établissement Français du Sang La Plaine Saint-Denis (EFS)-CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 ); ANR-15-CE12-0005,EpiSperm3,Bases moleculaires de la programmation post-méiotique du genome male(2015)
    • Publication Information:
      CCSD
      Wiley
    • Publication Date:
      2018
    • Collection:
      Université Grenoble Alpes: HAL
    • Abstract:
      International audience ; Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. R-CHOP is currently the standard therapy for DLBCL, but the prognosis of refractory or recurrent patients remains poor. In this study, we synthesized a new water-soluble antimalarial drug artemisinin derivative, SM1044. The treatment of DLBCL cell lines with SM1044 induces autophagy-dependent apoptosis, which is directed by an accelerated degradation of the antiapoptosis protein Survivin, via its acetylation-dependent interaction with the autophagy-related protein LC3-II. Additionally, SM1044 also stimulates the de novo synthesis of ceramide, which in turn activates the CaMKK2-AMPK-ULK1 axis, leading to the initiation of autophagy. Our findings not only elucidate the mechanism of autophagy-dependent apoptosis in DLBCL cells, but also suggest that SM1044 is a promising therapeutic molecule for the treatment of DLBCL, along with R-CHOP regimen.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/29277967; PUBMED: 29277967; PUBMEDCENTRAL: PMC5806110
    • Accession Number:
      10.1002/cam4.1276
    • Online Access:
      https://hal.science/hal-02325880
      https://hal.science/hal-02325880v1/document
      https://hal.science/hal-02325880v1/file/Cheng_et_al-2017.pdf
      https://doi.org/10.1002/cam4.1276
    • Rights:
      https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess
    • Accession Number:
      edsbas.514D84B