The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute (Articolo in rivista)

Type

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

Label

• The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute (Articolo in rivista) (literal)

Anno

• 2008-01-01T00:00:00+01:00 (literal)

Alternative label

• Chiarini F, Del Sole M, Mongiorgi S, Gaboardi GC, Cappellini A, Mantovani I, Follo MY, McCubrey JA, Martelli AM. (2008)
  The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute
  in Leukemia
  (literal)

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

• Chiarini F, Del Sole M, Mongiorgi S, Gaboardi GC, Cappellini A, Mantovani I, Follo MY, McCubrey JA, Martelli AM. (literal)

Pagina inizio

• 1106 (literal)

Pagina fine

• 1116 (literal)

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

• 22 (literal)

Rivista

• Leukemia (Rivista)

Note

• ISI Web of Science (WOS) (literal)

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

• Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Università, di Bologna, Bologna, Italy; Dipartimento di Scienze Motorie e della Salute, Università di Cassino, Cassino, Italy; Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA; IGM-CNR, Sezione di Bologna c/o I.O.R., Bologna, Italy. (literal)

Titolo

• The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute (literal)

Abstract

• A significant impediment to the success of cancer chemotherapy is the occurrence of multidrug resistance, which, in many cases, is attributable to overexpression of membrane transport proteins, such as the 170-kDa P-glycoprotein (P-gp). Also, upregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway is known to play an important role in drug resistance, and has been implicated in the aggressiveness of a number of different cancers, including T-acute lymphoblastic leukemia (T-ALL). We have investigated the therapeutic potential of the novel Akt inhibitor, perifosine (a synthetic alkylphospholipid), on human T-ALL CEM cells (CEM-R), characterized by both overexpression of P-gp and constitutive upregulation of the PI3K/Akt network. Perifosine treatment induced death by apoptosis in CEM-R cells. Apoptosis was characterized by caspase activation, Bid cleavage and cytochrome c release from mitochondria. The proapoptotic effect of perifosine was in part dependent on the Fas/FasL interactions and c-Jun NH(2)-terminal kinase (JNK) activation, as well as on the integrity of lipid rafts. Perifosine downregulated the expression of P-gp mRNA and protein and this effect required JNK activity. Our findings indicate that perifosine is a promising therapeutic agent for treatment of T-ALL cases characterized by both upregulation of the PI3K/Akt survival pathway and overexpression of P-gp. (literal)

Prodotto di

• Bersagli molecolari per il controllo della progressione tumorale (ME.P03.012.001) (Modulo)
• Institute of molecular genetics (IGM) (Istituto)

Autore CNR

• Alberto Maria Martelli (Unità di personale esterno)

Incoming links:

Prodotto

• Institute of molecular genetics (IGM) (Istituto)
• Bersagli molecolari per il controllo della progressione tumorale (ME.P03.012.001) (Modulo)

Autore CNR di

• Alberto Maria Martelli (Unità di personale esterno)

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

• Leukemia (Rivista)