HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma

Autor: M, Granato, V, Lacconi, M, Peddis, L V, Lotti, L, Di Renzo, L D, Renzo, R, Gonnella, R, Santarelli, P, Trivedi, L, Frati, G, D'Orazi, A, Faggioni, M, Cirone
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Cancer Research
Programmed cell death
Cell Survival
Immunology
Active Transport
Cell Nucleus

cathepsin D
Cathepsin D
Antineoplastic Agents
Biology
Permeability
Bid
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Lysosome
Cell Line
Tumor

Lymphoma
Primary Effusion

Pepstatins
medicine
Autophagy
Humans
HSP70 Heat-Shock Proteins
Protease Inhibitors
Propidium iodide
Sulfonamides
Apoptosis Inducing Factor
bid
cathepsin d
dendritic cells
pel
pes
Cell Biology
Dendritic Cells
PEL
medicine.disease
Cell biology
PES
medicine.anatomical_structure
chemistry
Apoptosis
Mitochondrial Membranes
Cancer research
Immunogenic cell death
Original Article
Primary effusion lymphoma
Drug Screening Assays
Antitumor

Lysosomes
Corrigendum
human activities
Pepstatin
BH3 Interacting Domain Death Agonist Protein
Zdroj: Cell Death & Disease
ISSN: 2041-4889
Popis: 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-μ, on primary effusion lymphoma (PEL) cell viability was analyzed. PES treatment induced a dose- and time-dependent 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 apoptosis-activating 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.
Databáze: OpenAIRE