ArticlePloS one2017
Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 60 citations in OpenAlex.
- Phytochemicals as Multitarget Therapeutics in Pancreatic Cancer: Mechanisms, Clinical Evidence, and Translational Challenges.Phytotherapy research : PTR · 2026Review
- Natural Compounds as Epimodulators in Epithelial Ovarian Cancer.Epigenomes · 2026Review
- A Narrative Review on Unravelling Bacterial-Mediated Carcinogenesis and Possible Alternative Treatment Strategies.BioMed research international · 2026Review
- Potential anticancer effects and toxicity of flavones luteolin and apigeninJournal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025Review
- MicroRNA-155 and its exosomal form: Small pieces in the gastrointestinal cancers puzzle.Cell biology and toxicology · 2024Review
- Regulation of cancer progression by CK2: an emerging therapeutic target.Medical oncology (Northwood, London, England) · 2024Review
- Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance.International journal of biological sciences · 2024Article
- Experimental evidence for anti-metastatic actions of apigenin: a mini review.Frontiers in oncology · 2024Review
- Modulatory Role of Phytochemicals/Natural Products in Cancer Immunotherapy.Current medicinal chemistry · 2024Review
- Phytochemicals as Immunomodulatory Molecules in Cancer Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Anti-cancerous effect of corn silk: a critical review on its mechanism of action and safety evaluation.3 Biotech · 2023Review
- Recent advancement in bioeffect, metabolism, stability, and delivery systems of apigenin, a natural flavonoid compound: challenges and perspectives.Frontiers in nutrition · 2023Review
- Active ingredients of traditional Chinese medicine for enhancing the effect of tumor immunotherapy.Frontiers in immunology · 2023Review
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Apigenin Targets MicroRNA-155, Enhances SHIP-1 Expression, and Augments Anti-Tumor Responses in Pancreatic Cancer.Cancers · 2022Article
- Immunomodulatory potential of natural products from herbal medicines as immune checkpoints inhibitors: Helping to fight against cancer via multiple targets.Medicinal research reviews · 2022Review
- Emerging role of Protein Kinase CK2 in Tumor immunity.Frontiers in oncology · 2022Review
- Article
- Recent insights into the biological functions of apigenin.EXCLI journal · 2020Article
- Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer.Frontiers in chemistry · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model. We also showed that this loss of Ikaros expression is associated with a significant decrease in CD4+ and CD8+ T cell percentages but increased CD4+CD25+ Tregs in TB mice. In this study, we evaluated the effects of the dietary flavonoid apigenin (API), on Ikaros expression and T cell immune responses. Treatment of splenocytes from naïve mice with (API) stabilized Ikaros expression and prevented Ikaros downregulation in the presence of murine Panc02 cells in vitro, similar to the proteasome inhibitor MG132. In vivo treatment of TB mice with apigenin (TB-API) improved survival, reduced tumor weights and prevented splenomegaly. API treatment also restored protein expression of some Ikaros isoforms, which may be attributed to its moderate inhibition of CK2 activity from splenocytes of TB-API mice. This partial restoration of Ikaros expression was accompanied by a significant increase in CD4+ and CD8+ T cell percentages and a reduction in Treg percentages in TB-API mice. In addition, CD8+ T cells from TB-API mice produced more IFN-γ and their splenocytes were better able to prime allogeneic CD8+ T cell responses compared to TB mice. These results provide further evidence that Ikaros is regulated by CK2 in our pancreatic cancer model. More importantly, our findings suggest that API may be a possible therapeutic agent for stabilizing Ikaros expression and function to maintain T cell homeostasis in murine PC.
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