Open AccessInduction of autophagy and autophagy‐dependent apoptosis in diffuse large B‐cell lymphoma by a new antimalarial artemisinin derivative, SM 1044
Author(s) -
Cheng Chunyan,
Wang Tao,
Song Zhiqun,
Peng Lijun,
Gao Mengqing,
Hermine Olivier,
Rousseaux Sophie,
Khochbin Saadi,
Mi JianQing,
Wang Jin
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1276
Subject(s) - autophagy , cancer research , chemistry , apoptosis , lymphoma , diffuse large b cell lymphoma , survivin , biology , immunology , biochemistry
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, SM 1044. The treatment of DLBCL cell lines with SM 1044 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 LC 3‐II. Additionally, SM 1044 also stimulates the de novo synthesis of ceramide, which in turn activates the Ca MKK 2– AMPK – ULK 1 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 SM 1044 is a promising therapeutic molecule for the treatment of DLBCL , along with R‐ CHOP regimen.