Apigenin, a dietary flavonoid, sensitizes human T cells for activation-induced cell death by inhibiting PKB/Akt and NF-κB activation pathway

Luting Xu, Li Zhang, Anne M. Bertucci, Richard M. Pope, Syamal K. Datta*

*Corresponding author for this work

Research output: Contribution to journalArticle

33 Scopus citations


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-κB activation and suppressing NF-κB-regulated anti-apoptotic molecules, cFLIP, Bcl-xL, Mcl-1, XIAP and IAP, but not Bcl-2. Apigenin suppressed NF-κB translocation to nucleus and inhibited IκBα 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-κB activation upon TCR stimulation, apigenin selectively inhibited PI3K-PKB/Akt, but not PKC-θ 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-κB activation, and especially cFLIP and COX-2 expression that are important for functioning and maintenance of immune cells in inflammation, autoimmunity and lymphoproliferation.

Original languageEnglish (US)
Pages (from-to)74-83
Number of pages10
JournalImmunology Letters
Issue number1
StatePublished - Nov 16 2008



  • Apoptosis
  • Autoimmunity
  • Human
  • Signal transduction
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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