Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis (Articolo in rivista) (literal)

Anno

• 2011-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1007/s10637-010-9475-6 (literal)

Alternative label

• Servida, F.; Lecis, D.; Scavullo, C.; Drago, C.; Seneci, P.; Carlo-Stella, C.; Manzoni, L.; Polli, E.;Deliliers, G. L.; Delia, D.; Onida, F. (2011)
  Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis
  in Investigational new drugs (Print)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Servida, F.; Lecis, D.; Scavullo, C.; Drago, C.; Seneci, P.; Carlo-Stella, C.; Manzoni, L.; Polli, E.;Deliliers, G. L.; Delia, D.; Onida, F. (literal)

Pagina inizio

• 1264 (literal)

Pagina fine

• 1275 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 29 (literal)

Rivista

• Investigational new drugs (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note

• DOI:10.1007/s10637-010-9475-6 (literal)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Servida, F.; Scavullo, C.; Polli, E.; Deliliers, G. L.; Onida, F. Università di Milano, Dipartimento di Farmacologia Chemioterapia & Tossicologia di Medicina, Fdn Matarelli, I-20129 Milan, Italy. Lecis, D.; Delia, D.; Fdn IRCCS Ist Nazl Tumori, Milan, Italy Drago, C.; Seneci, P.; Università di Milano, Dipartimento Chimica Organica e Industriale, Via Venezian 21, I-20129 Milan, Italy and CISI. Manzoni, L.; CNR - Istituto di Scienze e Tecnologie Molecolari, Via Golgi 19, I-20133 Milano, Italy (literal)

Titolo

• Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis (literal)

Abstract

• The Inhibitor of Apoptosis Proteins (IAPs) are important regulators of programmed cell death. XIAP is the most potent among them and is over-expressed in several hematological malignancies. Its activity is endogenously antagonized by SMAC/DIABLO, and also by small molecules mimicking Smac that can induce apoptosis in tumor cells. Here we describe the activity of 56 newly synthesized Smac-mimetics in human leukemic cell lines and normal CD34(+) progenitor cells. Our compounds bind to XIAP with high affinity, reduce the levels of cIAP1 and are cytotoxic at nanomolar or low micromolar concentrations. Furthermore, the Smac-mimetics synergize with Cytarabine, Etoposide and especially with TRAIL in combination treatments. Apoptosis activation was clearly detectable by the occurrence of sub G(1) apoptotic peak and the accumulation of cleaved PARP, caspase 8 and caspase 3. Interestingly, the down-regulation of XIAP sensitized Jurkat cells to drugs too, confirming the role of this protein in drug-resistance. In conclusion, while being very active in leukemic cells, our Smac-mimetics have modest effects on normal hematopoietic progenitors, suggesting their promising therapeutic potential as a new class of anticancer drugs in onco-hematology, particularly when combined with TRAIL, to overcome the resistance of cancer cells. (literal)

Prodotto di

• Ligandi integrinici per la diagnostica e terapia tumorale (PM.P01.021.005) (Modulo)
• Istituto di scienze e tecnologie molecolari (ISTM) (Istituto)

Autore CNR

• LEONARDO PIERPAOLO MANZONI (Unità di personale interno)

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• Parole chiave di "Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis" (Insieme di parole chiave)

Incoming links:

Prodotto

• Istituto di scienze e tecnologie molecolari (ISTM) (Istituto)
• Ligandi integrinici per la diagnostica e terapia tumorale (PM.P01.021.005) (Modulo)

Autore CNR di

• LEONARDO PIERPAOLO MANZONI (Unità di personale interno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Investigational new drugs (Rivista)

Insieme di parole chiave di

• Parole chiave di "Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis" (Insieme di parole chiave)