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

By Chunyan Cheng, Tao Wang, Zhiqun Song, Lijun Peng, Mengqing Gao, Olivier Hermine, Sophie Rousseaux, Saadi Khochbin, Jian-Qing Mi and Jin Wang

Abstract

International audienceDiffuse 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

Topics: Survivin, DLBCL, Apoptosis, artemisinin derivative, autophagy, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Publisher: 'Wiley'
Year: 2018
DOI identifier: 10.1002/cam4.1276
OAI identifier: oai:HAL:hal-02325880v1
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