We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma.
- Authors
Granato, M.; Lacconi, V.; Peddis, M.; Lotti, L. V.; Renzo, L. D.; Gonnella, R.; Santarelli, R.; Trivedi, P.; Frati, L.; D'Orazi, G.; Faggioni, A.; Cirone, M.
- Abstract
Heat-shock protein (HSP) 70 is aberrantly expressed in different malignancies and has a cancer-specific cell-protective effect. As such, it has emerged as a promising target for anticancer therapy. In this study, the effect of the HSP70-specific inhibitor (PES), also Pifitrin-l, on primary effusion lymphoma (PEL) cell viability was analyzed. PES treatment induced a dose- and timedependent cytotoxic effect in BC3 and BCBL1 PEL cells by inducing lysosome membrane permeabilization, relocation of cathepsin D in the cytosol, Bid cleavage, mitochondrial depolarization with release and nuclear translocation of apoptosisactivating factor. The PES-induced cell death in PEL cells was characterized by the appearance of Annexin-V/propidium iodide double-positive cells from the early times of treatment, indicating the occurrence of an additional type of cell death other than apoptosis, which, accordingly, was not efficiently prevented by the pan-caspase inhibitor Z-VAD-fmk. Conversely, PES-induced cell death was robustly reduced by pepstatin A, which inhibits Bid and caspase 8 processing. In addition, PES was responsible for a block of the autophagic process in PEL cells. Finally, we found that PES-induced cell death has immunogenic potential being able to induce dendritic cell activation.
- Publication
Cell Death & Disease, 2013, Vol 4, Issue 7, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/cddis.2013.263