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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2003

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating Protein Kinase C-alpha

Anno di pubblicazione: 2003

Formato: Elettronico Cartaceo

Autori: Russo M, Palumbo R, Mupo A, Tosto M, Iacomino G, Scognamiglio A, Tedesco I, Galano G, Russo GL.

Affiliazioni autori: Istituto Scienze dell'Alimentazione (ISA), CNR, Avellino

Autori CNR:

  • GIUSEPPE IACOMINO
  • ROSANNA PALUMBO
  • GIAN LUIGI RUSSO
  • MARIA RUSSO
  • IDOLO TEDESCO

Lingua: inglese

Abstract: We previously demonstrated that quercetin, a naturally occurring flavonoid with strong antioxidant properties, was able to enhance programmed cell death in HPB-acute lymphoblastic leukemia (ALL) cell line, derived from a human tymoma, when associated with the agonistic anti-CD95 monoclonal antibody. Here, we report that HPB-ALL cells are normally resistant to CD95-mediated apoptosis, and quercetin is able to sensitize this cell line through a mechanism independent of its antioxidant properties. In fact, other compounds structurally and functionally similar to quercetin, when associated with anti-CD95 antibody did not induce any CD95-mediated apoptosis, still maintaining their antioxidant capacity. We found that quercetin effects are mediated by the activation of PKCalpha. Treatment of HPB-ALL cells with quercetin slightly decreased PKCalpha activity, but when the flavonoid was associated with anti-CD95, the kinase activity increased by 12-fold with respect to the treatment with quercetin. In addition, overexpression of PKCalpha induced programmed cell death in the absence of any additional stimulus, while a kinase-defective mutant of PKCalpha was ineffective. Our data confirm the involvement of specific PKC isoforms in CD95 signaling and suggest, for the first time, that quercetin targets this pathway increasing apoptogenic response in a cell line resistant to CD95-mediated apoptosis.

Lingua abstract: inglese

Pagine da: 3330

Pagine a: 3342

Rivista:

Oncogene Macmillan,
Paese di pubblicazione: Regno Unito
Lingua: inglese
ISSN: 0950-9232

Numero volume: 22

DOI: 10.1038/sj.onc.1206493

Referee: Sė: Internazionale

Indicizzato da:

  • PubMed [12761503]
  • ISI Web of Science (WOS) [000183040000015]

Parole chiave:

  • apoptosi
  • quercetina
  • protein chinasi C
  • CD95/Fas/Apo1
  • flavonoidi

Altre informazioni: Free access at: http://www.nature.com/onc/journal/v22/n21/pdf/1206493a.pdf

Strutture CNR:

Moduli:

Allegati: Oncogene (2003) 22, 3330-3342 (application/pdf)

 
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