ArticleCell death & disease2014
Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 87 citations in OpenAlex.
- Humic substances enhance the anti-cancer efficacy of standard therapies.Cell death discovery · 2026Article
- 6-Methoxydihydrosanguinarine Suppresses the Proliferation of Non-small Cell Lung Cancer Cells through Elevation of ROS and Activation of IRE1/JNK Signaling.Cell biochemistry and biophysics · 2025Article
- Longikaurin A - Mediated Regulation of ROS/JNK Signaling Counteracts Epithelial-Mesenchymal Transition in Glioblastoma.Neuromolecular medicine · 2025Article
- Longikaurin A, a natural ent-kaurane, suppresses proliferation, invasion and tumorigenicity in oral squamous cell carcinoma cell by via inhibiting PI3K/Akt pathwayJournal of Cancer · 2025Article
- Exploring the Therapeutic Effects ofNutrients · 2024Article
- SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.Frontiers in oncology · 2024Review
- Charting the Evolution of Chemoenzymatic Strategies in the Syntheses of Complex Natural Products.Journal of the American Chemical Society · 2023Review
- Ternifolipyrons A-J: new cytotoxic α-pyrones fromRSC advances · 2023Article
- Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.International journal of molecular sciences · 2023Review
- Network Pharmacology and Molecular Docking Reveal the Mechanism ofDrug design, development and therapy · 2023Article
- Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review.Frontiers in pharmacology · 2023Review
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Recent Progress in Understanding the Action of Natural Compounds at Novel Therapeutic Drug Targets for the Treatment of Liver Cancer.Frontiers in oncology · 2021Review
- It takes two to tango: coupling of Hippo pathway and redox signaling in biological process.Cell cycle (Georgetown, Tex.) · 2020Review
- Divergent synthesis of complex diterpenes through a hybrid oxidative approach.Science (New York, N.Y.) · 2020Article
- Paeoniflorin inhibits cell viability and invasion of liver cancer cells via inhibition of Skp2.Oncology letters · 2020Article
- Mechanistic Pathways and Molecular Targets of Plant-Derived AnticancerBiomolecules · 2020Review
- Dioscin: A new potential inhibitor of Skp2 for cancer therapy.EBioMedicine · 2020Article
- Transcriptomic analysis reveals the oncogenic role of S6K1 in hepatocellular carcinoma.Journal of Cancer · 2020Article
- Cdh1-mediated Skp2 degradation by dioscin reprogrammes aerobic glycolysis and inhibits colorectal cancer cells growth.EBioMedicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and is also highly resistant to conventional chemotherapy treatments. In this study, we report that Longikaurin A (LK-A), an ent-kaurane diterpenoid isolated from the plant Isodon ternifolius, induced cell cycle arrest and apoptosis in human HCC cell lines. LK-A also suppressed tumor growth in SMMC-7721 xenograft models, without inducing any notable major organ-related toxicity. LK-A treatment led to reduced expression of the proto-oncogene S phase kinase-associated protein 2 (Skp2) in SMMC-7721 cells. Lower Skp2 levels correlated with increased expression of p21 and p-cdc2 (Try15), and a corresponding decrease in protein levels of Cyclin B1 and cdc2. Overexpression of Skp2 significantly inhibited LK-A-induced cell cycle arrest in SMMC-7721 cells, suggesting that LK-A may target Skp2 to arrest cells at the G2/M phase. LK-A also induced reactive oxygen species (ROS) production and apoptosis in SMMC-7721 cells. LK-A induced phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase and P38 MAP kinase. Treatment with, the JNK inhibitor SP600125 prevented LK-A-induced apoptosis in SMMC-7721 cells. Moreover, the antioxidant N-acetylcysteine prevented phosphorylation of both JNK and c-Jun. Taken together, these data indicate that LK-A induces cell cycle arrest and apoptosis in cancer cells by dampening Skp2 expression, and thereby activating the ROS/JNK/c-Jun signaling pathways. LK-A is therefore a potential lead compound for development of antitumor drugs targeting HCC.
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.