17-DMAG disrupted the autophagy flux leading to the apoptosis of acute lymphoblastic leukemia cells by inducing heat shock cognate protein 70

Life Sciences
Gang XuYang Fan

Abstract

B-lineage acute lymphoblastic leukemia (B-ALL) is most common in children. We had reported heat shock protein 90 (Hsp90) over-expressed in high risk B-ALL children. 17-DMAG is a water soluble Hsp90 inhibitor, which was proved to be effective for advanced solid tumors and hematological malignancy. However, there is little research on its application in newly diagnosed B-ALL. And the detailed mechanism is seldom discussed. Primary blast cells from 24 newly diagnosed B-ALL pediatric patients and two B-ALL cell lines were used in this study. Cell viability was measured by MTS assay. Apoptosis was evaluated by flow cytometry after annexin V-PI double staining. Protein expression was detected by immunoblotting analysis and immunofluorescence imaging. Cyto-ID autophagy detection assay was performed to show the autophagosomes and LysoTracker labeling to show the lysosomes. Gene knockdown was performed by RNA interference, and mRNA expression was measured by RT-qPCR. We showed 17-DMAG induced apoptosis in newly diagnosed B-ALL blasts and cell lines effectively. 17-DMAG induced heat shock cognate protein 70 (Hsc70) expression significantly. High expressed Hsc70 inhibited cathepsin D post-transcriptionally to impede the autophagic flux, w...Continue Reading

Citations

Oct 31, 2020·International Journal of Molecular Sciences·Alessia MongelliCarlo Gaetano
Mar 2, 2021·Frontiers in Oncology·Javiera RiosMauricio Budini

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