Tier 4 — mechanistic

Enhancement of p53 Expression in Keratinocytes by the Bioflavonoid Apigenin Is Associated with RNA-binding Protein HuR

Xin Tong, Jill C. Pelling
Molecular Carcinogenesis 2009 48(2):118-129

Bibliography

PubMed
PMID 18680106
PubMed Central
PMC2631086
DOI
10.1002/mc.20460
Funding
Supported by NIH grants CA072987 and CA104768 to Jill C. Pelling and by the Zell Foundation.
Competing interests
A competing-interests statement was not identified in the uploaded manuscript.

Study snapshot

DesignMechanistic in vitro cell-culture study using protein, RNA, reporter-gene, overexpression and siRNA experiments
ModelMouse 308 keratinocyte cell line with wild-type p53
SampleCell-culture experiments performed with repeated independent assays; not a human or animal intervention trial.
InterventionApigenin across 0-70 micromolar concentrations; many mechanistic experiments used 50 micromolar apigenin for 4-8 hours.
DurationAcute cell exposure over hours.
Endpointsp53 protein expression and nascent synthesis; HuR cytoplasmic localization; HuR-p53 mRNA association; p53 3-prime UTR reporter activity; p16 expression; Effects of HuR and p16 knockdown

What the study showed, in plain terms

Apigenin increased p53 protein in cultured mouse keratinocytes not mainly by making more p53 mRNA, but by increasing translation of existing p53 mRNA. The RNA-binding protein HuR was central to this response: apigenin moved more HuR into the cytoplasm and increased HuR binding to p53 mRNA.

Key findings

Apigenin increased nascent p53 synthesis and HuR association with p53 mRNA. HuR overexpression strengthened the p53 response, whereas HuR knockdown reduced both total p53 induction and new p53 synthesis. Apigenin also increased p16, and p16 knockdown reduced apigenin-induced cytoplasmic HuR localization.

What this study can and cannot tell us

The experiments were performed in an initiated mouse keratinocyte cell line at micromolar concentrations. They do not establish that orally consumed apigenin reaches comparable tissue concentrations, activates this pathway in humans or prevents cancer clinically.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology