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536932 
Journal Article 
Apigenin, a dietary flavonoid, sensitizes human T cells for activation-induced cell death by inhibiting PKB/Akt and NF-kappa B activation pathway 
Xu, LT; Zhang, L; Bertucci, AM; Pope, RM; Datta, SK 
2008 
Yes 
Immunology Letters
ISSN: 0165-2478
EISSN: 1879-0542 
121 
1 
74-83 
English 
18812189 
WOS:000261280600011 
Resistance of T cells to activation-induced cell death (AICD) is associated with autoimmunity and lymphoproliferation. We found that apigenin (4',5,7-trihydroxyflavone), a non-mutagenic dietary flavonoid, augmented both extrinsic and intrinsic pathways of apoptosis in recurrently activated, but not in primarily stimulated, human blood CD4+ T cells. Apigenin potentiated AICD by inhibiting NF-kappa B activation and suppressing NF-kappa B-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2. Apigenin suppressed NF-kappa B translocation to nucleus and inhibited I kappa B alpha phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines. Among the pathways that lead to NF-kappa B activation upon TCR stimulation, apigenin selectively inhibited PI3K-PKB/Akt, but not PKC-theta activation in the human T cells, and synergized with a PI3K inhibitor to markedly augment AICD. Apigenin also suppressed expression of anti-apoptotic cyclooxygenase 2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase. Thus, in chronically activated human T cells, relatively non-toxic apigenin can Suppress anti-apoptotic pathways involving NF-kappa B activation, and especially cFLIP and COX-2 expression that are important for functioning and maintenance of immune cells in inflammation, autoimmunity and lymphoproliferation. (C) 2008 Elsevier B.V. All rights reserved. 
Apoptosis; T cells; Human; Signal transduction; Autoimmunity; kinase-c-theta; systemic-lupus-erythematosus; mediated apoptosis; immune-system; in-vivo; lymphocyte homeostasis; signaling complex; leukemia-cells; up-regulation; expression