citations

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

Authors:

Cheng C, Wang T, Song Z, Peng L, Gao M, Hermine O, Rousseaux S, Khochbin S, Mi JQ, Wang J.

In:

Source: Cancer Medicine
Publication Date: (2017)
Issue: 7: 2

Research Area:

Cancer Research/Cell Biology

Cells used in publication:

SU-DHL-4: Species: human; Tissue Origin: blood
OCI-LY-3: Species: human; Tissue Origin:

Platform:

4D-Nucleofector® X-Unit

Experiment

Cells were centrifuged at 90g for 10 min, the supernatants were removed, the cell pellets were resuspended in 4D-Nucleofector^™ solution (SF cell line 4D-Nucleofector X kit L, Lonza, Basel, Switzerland) containing the plasmids and transferred into the Nucleocuvette^™ vessels. The vessels were then placed into the retainer of the 4D-Nucleofector^™ X unit and the Nucleofection^™ process was ran with program DN-100. After the run completed, the vessels were removed from the retainer and incubated for 10 min. The cells were resuspended with prewarmed medium and mixed by pipetting for three times, then plated onto cell culture plates for further experiments.

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, 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.

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