ArticleCancer science2019
Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia-inducible factor 1α axis.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Efficacy and safety of cinobufacini capsules combined with oxaliplatin-based chemotherapy for advanced colorectal cancer: a human systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- A narrative review of cinobufacini for endometrial cancer: mechanisms and therapeutic implications.Translational cancer research · 2026Review
- Cinobufagin as a Potential Intervention Against Liver Cancer-A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A dual-drug strategy to enhance the function of cryopreserved ovaries by promoting revascularization and inhibiting follicle over-activation.Reproductive biology and endocrinology : RB&E · 2025Article
- Cinobufagin: Unveiling the hidden bufadienolide's promise in combating alimentary canal cancer development and progression - a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Efficacy and safety of cinobufacin-based combination therapy for advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials.Discover oncology · 2025Article
- Cinobufagin Inhibits Invasion and Migration of Non-Small Cell Lung Cancer via Regulating Glucose Metabolism Reprogramming in Tumor-Associated Macrophages.Drug design, development and therapy · 2025Article
- Targeted lipidomics meets transcriptomics: how cinobufagin rewires fatty acid, sphingolipid, and glycerophospholipid metabolism to combat hepatoma cell growth.Frontiers in pharmacology · 2025Article
- Promotion of Random Flap Neovascularisation in Rats with Diabetes Using Botulinum Toxin Type A Through the HIF-1α/VEGF Pathway.Clinical, cosmetic and investigational dermatology · 2025Article
- Cinobufagin disrupts the stability of lipid rafts by inhibiting the expression of caveolin-1 to promote non-small cell lung cancer cell apoptosis.Archives of medical science : AMS · 2024Article
- Anthracycline chemicals with anthracyclinone structure exert antitumor effects by inhibiting angiogenesis and lymphangiogenesis in a xenografted gastric tumor model.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Mechanism of the HIF-1α/VEGF/VEGFR-2 pathway in the proliferation and apoptosis of human haemangioma endothelial cells.International journal of experimental pathology · 2023Article
- Pharmacological Effects of Cinobufagin.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Toad venom-derived bufadienolides and their therapeutic application in prostate cancers: Current status and future directions.Frontiers in chemistry · 2023Review
- Cinobufagin induces acute promyelocytic leukaemia cell apoptosis and PML-RARA degradation in a caspase-dependent manner by inhibiting the β-catenin signalling pathway.Pharmaceutical biology · 2022Article
- Bioactive constituents of animal-derived traditional Chinese medicinal materials for breast cancer: opportunities and challenges.Journal of Zhejiang University. Science. B · 2022Review
- Effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in a rat bladder tumor model.Translational andrology and urology · 2022Article
- Combining Network Pharmacology and Experimental Validation to Study the Action and Mechanism of Water extract of Asparagus Against Colorectal Cancer.Frontiers in pharmacology · 2022Article
- A research update on the antitumor effects of active components of Chinese medicine ChanSu.Frontiers in oncology · 2022Review
- Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Inducing angiogenesis is a hallmark of cancers that sustains tumor growth and metastasis. Neovascularization is a surprisingly early event during the multistage progression of cancer. Cinobufagin, an important bufadienolide originating from Chan Su, has been clinically used to treat cancer in China since the Tang dynasty. Here, we show that cinobufagin suppresses colorectal cancer (CRC) growth in vivo by downregulating angiogenesis. The hierarchized neovasculature is significantly decreased and the vascular network formation is disrupted in HUVEC by cinobufagin in a dose-dependent way. Endothelial apoptosis is observed by inducing reactive oxygen species (ROS) accumulation and mitochondrial dysfunction which can be neutralized by N-acetyl-l-cysteine (NAC). Expression of hypoxia-inducible factor 1α (HIF-1α) is reduced and phosphorylation of mTOR at Ser2481 and Akt at Ser473 is downregulated in HUVEC. Endothelial apoptosis is triggered by cinobufagin by stimulation of Bax and cascade activation of caspase 9 and caspase 3. Increased endothelial apoptosis rate and alterations in the HIF-1α/mTOR pathway are recapitulated in tumor-bearing mice in vivo. Further, the anti-angiogenesis function of cinobufagin is consolidated based on its pro-apoptotic effects on an EOMA-derived hemangioendothelioma model. In conclusion, cinobufagin suppresses tumor neovascularization by disrupting the endothelial mTOR/HIF-1α pathway to trigger ROS-mediated vascular endothelial cell apoptosis. Cinobufagin is a promising natural anti-angiogenetic drug that has clinical translation potential and practical application value.
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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.