ArticleActa pharmacologica Sinica2025
Aristolochic acids-hijacked p53 promotes liver cancer cell growth by inhibiting ferroptosis.
Article in Acta pharmacologica Sinica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- 3-Hydroxydehydroleucodin ameliorates neuroinflammation and ischemic brain injury by blocking the TRIM21-PRDX1 interaction.Acta pharmacologica Sinica · 2026Article
- Salvianolic Acid B Upregulates miR-744-5p Expression in Peripheral Blood Mononuclear Cell-Derived Extracellular Vesicles to Alleviate Uremic Cardiomyopathy.Journal of extracellular vesicles · 2026Article
- Targeting Cuproptosis and Ferroptosis via a ROS-Responsive Nanoplatform for Enhanced Synergistic Therapy Against Hepatocellular Carcinoma.Antioxidants (Basel, Switzerland) · 2026Article
- A Dual-Gene Signature of PMAIP1 and GADD45A for Early Detection of Intrahepatic Cholangiocarcinoma in the Context of Primary Sclerosing Cholangitis.International journal of molecular sciences · 2026Article
- Aristolochic Acid and Hepatocellular Carcinoma: A Critical Review of Genotoxic and Inflammatory Mechanisms.International journal of molecular sciences · 2026Review
- Bone marrow-derived mesenchymal stem cells alleviate hepatic lipid metabolism disorders after scald injury: integrating liver transcriptome and metabolome.Stem cell research & therapy · 2026Article
- 3-hydroxyanthranilic acid suppresses colorectal cancer growth and enhances 5-fluorouracil sensitivity via the YY1-p53 and YY1-DKK4 axes.Frontiers in pharmacology · 2026Article
- Targeting ferroptosis by noncoding RNAs as a novel therapeutic strategy for hepatocellular carcinoma.Discover oncology · 2025Review
- Lactylation-mediated miRNA regulation in cancer therapy resistance.Journal of translational medicine · 2025Review
- Synthesis and Cytotoxicity Evaluation of Denitroaristolochic Acids: Structural Insights and Mechanistic Implications in Nephrotoxicity.Biomolecules · 2025Article
- The role of ferroptosis in Alzheimer's disease: Mechanisms and therapeutic potential (Review).Molecular medicine reports · 2025Review
- Growth Arrest and DNA Damage Protein 45A Promotes PPRV Replication via the Downregulation of TBK1 Expression to Inhibit IFN-β Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- LZTS2 methylation as a potential diagnostic and prognostic marker in LIHC and STAD: Evidence from bioinformatics and in vitro analyses.Scientific reports · 2025Article
- CD155 promotes the advancement of hepatocellular carcinoma by suppressing the p53-mediated ferroptosis via interacting with CD96.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Copper metabolism and cuproptosis: broad perspectives in the treatment of hepatocellular carcinoma.Frontiers in oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aristolochic acids (AAs) have been identified as a significant risk factor for hepatocellular carcinoma (HCC). Ferroptosis is a type of regulated cell death involved in the tumor development. In this study, we investigated the molecular mechanisms by which AAs enhanced the growth of HCC. By conducting bioinformatics and RNA-Seq analyses, we found that AAs were closely correlated with ferroptosis. The physical interaction between p53 and AAs in HepG2 cells was validated by bioinformatics analysis and SPR assays with the binding pocket sites containing Pro92, Arg174, Asp207, Phe212, and His214 of p53. Based on the binding pocket that interacts with AAs, we designed a mutant and performed RNA-Seq profiling. Interestingly, we found that the binding pocket was responsible for ferroptosis, GADD45A, NRF2, and SLC7A11. Functionally, the interaction disturbed the binding of p53 to the promoter of GADD45A or NRF2, attenuating the role of p53 in enhancing GADD45A and suppressing NRF2; the mutant did not exhibit the same effects. Consequently, this event down-regulated GADD45A and up-regulated NRF2, ultimately inhibiting ferroptosis, suggesting that AAs hijacked p53 to down-regulate GADD45A and up-regulate NRF2 in HepG2 cells. Thus, AAs treatment resulted in the inhibition of ferroptosis via the p53/GADD45A/NRF2/SLC7A11 axis, which led to the enhancement of tumor growth. In conclusion, AAs-hijacked p53 restrains ferroptosis through the GADD45A/NRF2/SLC7A11 axis to enhance tumor growth. Our findings provide an underlying mechanism by which AAs enhance HCC and new insights into p53 in liver cancer. Therapeutically, the oncogene NRF2 is a promising target for liver cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.