http://www.cnr.it/ontology/cnr/individuo/prodotto/ID45534

Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating Protein Kinase C-alpha (Articolo in rivista)

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Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating Protein Kinase C-alpha (Articolo in rivista) (literal)

Anno

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Alternative label

Russo M, Palumbo R, Mupo A, Tosto M, Iacomino G, Scognamiglio A, Tedesco I, Galano G, Russo GL. (2003)
Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating Protein Kinase C-alpha
in Oncogene (Basingstoke)
(literal)

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

Russo M, Palumbo R, Mupo A, Tosto M, Iacomino G, Scognamiglio A, Tedesco I, Galano G, Russo GL. (literal)

Pagina inizio

Pagina fine

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Free access at: http://www.nature.com/onc/journal/v22/n21/pdf/1206493a.pdf (literal)

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Rivista

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R. Palumbo, ricercatrice CNR, era affiliata a questo Istituto all'epoca di questo lavoro. (literal)

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Il lavoro descrive la capacità della quercetina, un flavonoide naturale presente in molti alimenti della dieta mediterranea, di rendere sensibili cellule leucemiche all'apoptosi(morte cellulare programmata) indotta dall'attivazione del recettore CD95/Fas/Apo1. Normalmente, tali cellule, così come molte altre linee tumorali, sono resistenti all'azione pro-apoptotica di CD95. La presenza della quercetina, in associazione a CD95 ristabilisce un'efficae ed irreversibile risposta apoptotica. Il lavoro descrive il meccanismo d'azione della quercetina che coinvolge, tra l'altro, l'attivazione della proteina chinasi PKC-alfa. (literal)

Note

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Titolo

Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating Protein Kinase C-alpha (literal)

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. (literal)

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