ArticleOncogene2019
DHS (trans-4,4'-dihydroxystilbene) suppresses DNA replication and tumor growth by inhibiting RRM2 (ribonucleotide reductase regulatory subunit M2).
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 63 citations in OpenAlex.
- Decreased expression of ribonucleotide reductase M2 accelerates ovarian aging by suppressing cell proliferation and inducing DNA damage in mouse theca-interstitial cells.Journal of ovarian research · 2026Article
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- The role of cytokines in ovarian cancer drug resistance.International journal of cancer · 2026Review
- AntagomiR-192-5p-engineered exosomes encapsulated in MXene-modified GelMA hydrogel facilitated epithelization of burn wounds by targeting OLFM4.Bioactive materials · 2025Article
- Synergistic effects of the curcumin analog HO-3867 and olaparib in transforming fallopian tube epithelial cells.Investigational new drugs · 2025Article
- Integration of scRNA-seq and ST-seq identifies hyperproliferative RRM2+ cells features and therapeutic targets in gastric cancer.Journal of translational medicine · 2025Article
- Ribonucleotide reductase (RNR) inhibitors as target-based weapon for future cancer drug development.Future medicinal chemistry · 2025Review
- Targeting Replication Fork Processing Synergizes with PARP Inhibition to Potentiate Lethality in Homologous Recombination Proficient Ovarian Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Significance of Ribonucleoside-diphosphate Reductase Subunit M2 in Lung Adenocarcinoma.Current gene therapy · 2025Article
- Polyphenols in Pancreatic Cancer Management: Exploring the Roles and Mechanisms of Resveratrol and Epigallocatechin.Oncology research · 2025Review
- Ribonucleotide reductase small subunit M2 promotes the proliferation of esophageal squamous cell carcinoma cellsActa pharmaceutica Sinica. B · 2024Article
- Stilbene Treatment Reduces Stemness Features in Human Lung Adenocarcinoma Model.International journal of molecular sciences · 2024Article
- A proteasome-dependent inhibition of SIRT-1 by the resveratrol analogue 4,4'-dihydroxy-Journal of traditional and complementary medicine · 2024Article
- Deciphering the Molecular Complexity of Hepatocellular Carcinoma: Unveiling Novel Biomarkers and Therapeutic Targets Through Advanced Bioinformatics Analysis.Cancer reports (Hoboken, N.J.) · 2024Article
- Review
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- A comprehensive analysis of ribonucleotide reductase subunit M2 for carcinogenesis in pan-cancer.PloS one · 2024Article
- RRM2‑mediated Wnt/β‑catenin signaling pathway activation in lung adenocarcinoma: A potential prognostic biomarker.Oncology letters · 2023Article
- [PRMT1 inhibits apoptosis of nasopharyngeal carcinoma cells by promoting RRM2 expression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- The putative oncogenic role of WDTC1 in colorectal cancer.Carcinogenesis · 2022Article
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 at 7 institutions in 2 countries.
Funding
Abstract
DNA replication machinery is responsible for accurate and efficient duplication of the chromosome. Since inhibition of DNA replication can lead to replication fork stalling, resulting in DNA damage and apoptotic death, inhibitors of DNA replication are commonly used in cancer chemotherapy. Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the biosynthesis of deoxyribonucleoside triphosphates (dNTPs) that are essential for DNA replication and DNA damage repair. Gemcitabine, a nucleotide analog that inhibits RNR, has been used to treat various cancers. However, patients often develop resistance to this drug during treatment. Thus, new drugs that inhibit RNR are needed to be developed. In this study, we identified a synthetic analog of resveratrol (3,5,4'-trihydroxy-trans-stilbene), termed DHS (trans-4,4'-dihydroxystilbene), that acts as a potent inhibitor of DNA replication. Molecular docking analysis identified the RRM2 (ribonucleotide reductase regulatory subunit M2) of RNR as a direct target of DHS. At the molecular level, DHS induced cyclin F-mediated down-regulation of RRM2 by the proteasome. Thus, treatment of cells with DHS reduced RNR activity and consequently decreased synthesis of dNTPs with concomitant inhibition of DNA replication, arrest of cells at S-phase, DNA damage, and finally apoptosis. In mouse models of tumor xenografts, DHS was efficacious against pancreatic, ovarian, and colorectal cancer cells. Moreover, DHS overcame both gemcitabine resistance in pancreatic cancer and cisplatin resistance in ovarian cancer. Thus, DHS is a novel anti-cancer agent that targets RRM2 with therapeutic potential either alone or in combination with other agents to arrest cancer development.
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.