Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating protein kinase Cα(798 views) Russo M, Palumbo R, Mupo A, Tosto M, Iacomino G, Scognamiglio A, Tedesco I, Galano G, Russo GL
Keywords: Apoptosis, Cd95 Fas Apo1, Flavonoids, Hpb-All, Pkcα, Quercetin, Antioxidant, Fas Antigen, Isoenzyme, Monoclonal Antibody, Mutant Protein, Protein Kinase C Alpha, Reactive Oxygen Metabolite, Antineoplastic Agent, Caspase, Prkca Protein, Human, Acute Lymphocytic Leukemia, Antioxidant Activity, Article, Cell Assay, Cell Death, Cell Viability, Controlled Study, Cytotoxicity, Drug Effect, Drug Mechanism, Enzyme Activation, Enzyme Activity, Enzyme Assay, Human Cell, Leukemia Cell Line, Priority Journal, Protein Expression, Sensitization, Signal Transduction, Cell Culture, Enzymology, Immunology, Pathology, Antibodies, Jurkat Cells, Protein Kinase C-Alpha, Tumor Cells,
Affiliations: *** IBB - CNR ***
Ist. di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche, 83100 Avellino, Italy
Stazione Zoologica 'Anton Dohrn', 80121 Napoli, Italy
References: Not available.
Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating protein kinase Cα
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 PKCα. Treatment of HPB-ALL cells with quercetin slightly decreased PKCα 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 PKCα induced programmed cell death in the absence of any additional stimulus, while a kinase-defective mutant of PKCα 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.
Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating protein kinase Cα