Induction of autophagy and autophagy‐dependent apoptosis in diffuse large B‐cell lymphoma by a new antimalarial artemisinin derivative, <scp>SM</scp>1044

Abstract

Abstract 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.