{"id":2646,"date":"2002-02-20T10:10:00","date_gmt":"2002-02-20T09:10:00","guid":{"rendered":"http:\/\/www.isidorolab.com\/public\/?p=2646"},"modified":"2021-09-05T10:17:27","modified_gmt":"2021-09-05T08:17:27","slug":"lysosomal-proteases-as-potential-targets-for-the-induction-of-apoptotic-cell-death-in-human-neuroblastomas","status":"publish","type":"post","link":"http:\/\/www.isidorolab.com\/public\/index.php\/2002\/02\/20\/lysosomal-proteases-as-potential-targets-for-the-induction-of-apoptotic-cell-death-in-human-neuroblastomas\/","title":{"rendered":"Lysosomal proteases as potential targets for the induction of apoptotic cell death in human neuroblastomas"},"content":{"rendered":"\t\t
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Roberta Castino<\/a>\u00a0 1 <\/a><\/sup>,\u00a0Deborah Pace<\/a>,\u00a0Marina D\u00e9moz<\/a>,\u00a0Marco Gargiulo<\/a>,\u00a0Chiara Ariatta<\/a>,\u00a0Elisabetta Raiteri<\/a>,\u00a0Ciro Isidoro<\/a><\/p>\n\n

Affiliation<\/h3>\n\n
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1<\/sup> Dipartimento di Scienze Mediche, Laboratorio di Patologia Molecolare, Universit\u00e0 A. Avogadro, Novara, Italy.<\/p>\n

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PMID: 11857353<\/strong><\/p>\n

DOI: 10.1002\/ijc.10139<\/a><\/p>\n

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Abstract<\/h2>\n\n

Neuroblastoma is the most common type of cancer in infants. In children this tumor is particularly aggressive; despite various new therapeutic approaches, it is associated with poor prognosis. Given the importance of endosomal-lysosomal proteolysis in cellular metabolism, we hypothesized that inhibition of lysosomal protease would impact negatively on neuroblastoma cell survival. Treatment with E-64 or CA074Me (2 specific inhibitors of cathepsin B) or with pepstatin A (a specific inhibitor of cathepsin D) was cytotoxic for 2 neuroblastoma cell lines having different degrees of malignancy. Cell death was associated with condensation and fragmentation of chromatin and externalization of plasma membrane phosphatidylserine, 2 hallmarks of apoptosis. Concomitant inhibition of the caspase cascade protected neuroblastoma cells from cathepsin inhibitor-induced cytotoxicity. These data indicate that prolonged inhibition of the lysosomal proteolytic pathway is incompatible with cell survival, leading to apoptosis of neuroblastoma cells, and that the cathepsin-mediated and caspase-mediated proteolytic systems are connected and cooperate in the regulation of such an event. Since modern antitumor chemotherapy is aimed at restoring the normal rate of apoptosis in neoplastic tissues, the demonstration that endosomal-lysosomal cathepsins are involved in this process may constitute a basis for novel strategies that include cathepsin inhibitors in the therapeutic regimen.<\/p>\n\n

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Copyright 2001 Wiley-Liss, Inc.<\/p>\n<\/div><\/div>\n<\/div>\n<\/div>\n\n

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Roberta Castino  1 , Deborah Pace, Marina D\u00e9moz, Marco Gargiulo, Chiara Ariatta, Elisabetta Raiteri, Ciro Isidoro Affiliation 1 Dipartimento di Scienze Mediche, Laboratorio di Patologia Molecolare, Universit\u00e0 A. Avogadro, Novara, Italy. \u00a0 PMID: 11857353 DOI: 10.1002\/ijc.10139 \u00a0 Abstract Neuroblastoma is the most common type of cancer in infants. In children this tumor is particularly aggressive; despite various new therapeutic approaches, it…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"yasr_overall_rating":0,"yasr_post_is_review":"","yasr_auto_insert_disabled":"","yasr_review_type":"","footnotes":""},"categories":[136],"tags":[55],"class_list":["post-2646","post","type-post","status-publish","format-standard","hentry","category-paper","tag-cancer"],"yoast_head":"\r\nLysosomal proteases as potential targets for the induction of apoptotic cell death in human neuroblastomas - IsidoroLab<\/title>\r\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\r\n<link rel=\"canonical\" href=\"http:\/\/www.isidorolab.com\/public\/index.php\/2002\/02\/20\/lysosomal-proteases-as-potential-targets-for-the-induction-of-apoptotic-cell-death-in-human-neuroblastomas\/\" \/>\r\n<meta property=\"og:locale\" content=\"it_IT\" \/>\r\n<meta property=\"og:type\" content=\"article\" \/>\r\n<meta property=\"og:title\" content=\"Lysosomal proteases as potential targets for the induction of apoptotic cell death in human neuroblastomas - IsidoroLab\" \/>\r\n<meta property=\"og:description\" content=\"Roberta Castino  1 , Deborah Pace, Marina D\u00e9moz, Marco Gargiulo, Chiara Ariatta, Elisabetta Raiteri, Ciro Isidoro Affiliation 1 Dipartimento di Scienze Mediche, Laboratorio di Patologia Molecolare, Universit\u00e0 A. 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