ArticleBiochemical pharmacology2012
Apigenin induces DNA damage through the PKCδ-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair.
Article in Biochemical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Natural Products as Modulators of the DNA Damage Response and Oncogenic Signaling in Breast Cancer Therapy.International journal of molecular sciences · 2026Review
- Potential of Apigenin, Berberine, Chrysin, and Luteolin to Overcome Doxorubicin Resistance in Acute Promyelocytic Leukemia HL-60 Cells.International journal of molecular sciences · 2025Article
- Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading.International journal of molecular sciences · 2024Review
- A Multimodel Study of the Role of Novel PKC Isoforms in the DNA Integrity Checkpoint.International journal of molecular sciences · 2023Article
- Role of Induced Programmed Cell Death in the Chemopreventive Potential of Apigenin.International journal of molecular sciences · 2022Review
- Ibrutinib Blocks YAP1 Activation and Reverses BRAF Inhibitor Resistance in Melanoma Cells.Molecular pharmacology · 2022Article
- The CWI Pathway: A Versatile Toolbox to Arrest Cell-Cycle Progression.Journal of fungi (Basel, Switzerland) · 2021Review
- Urban living in healthy Tanzanians is associated with an inflammatory status driven by dietary and metabolic changes.Nature immunology · 2021Article
- Apigenin by targeting hnRNPA2 sensitizes triple-negative breast cancer spheroids to doxorubicin-induced apoptosis and regulates expression of ABCC4 and ABCG2 drug efflux transporters.Biochemical pharmacology · 2020Article
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity.Molecules (Basel, Switzerland) · 2020Article
- The Targeted Impact of Flavones on Obesity-Induced Inflammation and the Potential Synergistic Role in Cancer and the Gut Microbiota.Molecules (Basel, Switzerland) · 2020Review
- Apigenin and hesperidin augment the toxic effect of doxorubicin against HepG2 cells.BMC pharmacology & toxicology · 2019Article
- Flavonoids: New Frontier for Immuno-Regulation and Breast Cancer Control.Antioxidants (Basel, Switzerland) · 2019Review
- Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Dietary compounds have potential in controlling atherosclerosis by modulating macrophage cholesterol metabolism and inflammation via miRNA.NPJ science of food · 2018Review
- HBXIP, a binding protein of HBx, regulates maintenance of the G2/M phase checkpoint induced by DNA damage and enhances sensitivity to doxorubicin-induced cytotoxicity.Cell cycle (Georgetown, Tex.) · 2017Article
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
- Flavones: From Biosynthesis to Health Benefits.Plants (Basel, Switzerland) · 2016Review
- Anticancer potential of the histone deacetylase inhibitor-like effects of flavones, a subclass of polyphenolic compounds: a review.Molecular biology reports · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti-carcinogenic activities through mechanisms yet not fully defined. In the present study, we show that the treatment of leukemia cells with apigenin resulted in the induction of DNA damage preceding the activation of the apoptotic program. Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta (PKCδ), yet was independent of reactive oxygen species or caspase activity. Treatment of monocytic leukemia cells with apigenin induced the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key regulators of the DNA damage response, without affecting the ataxia-telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and pharmacological inhibition of PKCδ abrogated ATM and H2AX phosphorylation, whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We established that apigenin delayed cell cycle progression at G1/S and increased the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that apigenin-induced DNA damage led to down-regulation of genes involved in cell-cycle control and DNA repair. Taken together, the present results show that the PKCδ-dependent activation of ATM and H2AX define the signaling networks responsible for the regulation of DNA damage promoting genome-wide mRNA alterations that result in cell cycle arrest, hence contributing to the anti-carcinogenic activities of this flavonoid.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.