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Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine

Nadine Nelson1, Karoly Szekeres1, Cristina Iclozan1

  • 1Department of Molecular Medicine, University of South Florida, Tampa, Florida, United States of America.

Plos One
|February 3, 2017
PubMed

Insights

Dietary apigenin (API) stabilizes the transcription factor Ikaros in pancreatic cancer (PC) models. API treatment improves survival and T cell responses, suggesting its therapeutic potential for PC immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Pancreatic cancer (PC) suppresses anti-tumor immunity by promoting regulatory T cells (Tregs).
  • The transcription factor Ikaros is crucial for T cell function and is downregulated in PC via protein degradation.
  • This Ikaros loss is linked to an imbalance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), favoring CK2 activity.

Purpose of the Study:

  • To investigate the effects of the dietary flavonoid apigenin (API) on Ikaros expression and T cell immunity in a murine PC model.
  • To determine if API can restore Ikaros function and improve anti-tumor immune responses.

Main Methods:

  • In vitro treatment of splenocytes with API and Panc02 cells.
  • In vivo administration of API to tumor-bearing (TB) mice.
  • Analysis of Ikaros expression, T cell populations (CD4+, CD8+, Tregs), and cytokine production (IFN-γ).
  • Assessment of CK2 activity in splenocytes.

Main Results:

  • Apigenin (API) stabilized Ikaros expression in vitro and in vivo.
  • API treatment improved survival, reduced tumor weight, and prevented splenomegaly in TB mice.
  • API partially restored Ikaros isoforms, reduced Tregs, and increased CD4+ and CD8+ T cells.
  • API-treated mice showed increased CD8+ T cell IFN-γ production and enhanced allogeneic T cell priming.

Conclusions:

  • Ikaros stability in PC is regulated by CK2, and apigenin (API) can counteract this.
  • API treatment restores T cell homeostasis and enhances anti-tumor immunity in a murine PC model.
  • Apigenin shows promise as a therapeutic agent for pancreatic cancer immunotherapy by stabilizing Ikaros.

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