ArticlePloS one2016
BJ-1108, a 6-Amino-2,4,5-Trimethylpyridin-3-ol Analog, Inhibits Serotonin-Induced Angiogenesis and Tumor Growth through PI3K/NOX Pathway.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.Clinical and translational medicine · 2024Review
- The 3D in vivo chorioallantoic membrane model and its role in breast cancer research.Journal of cancer research and clinical oncology · 2022Review
- G-Protein Coupled Receptor Signaling and Mammalian Target of Rapamycin Complex 1 Regulation.Molecular pharmacology · 2022Review
- Synthesis of Pyridoxine-Derived Dimethylpyridinols Fused with Aminooxazole, Aminoimidazole, and Aminopyrrole.Molecules (Basel, Switzerland) · 2022Article
- Association between antipsychotic agents and risk of lung cancer: a nested case-control study.Cancer communications (London, England) · 2022Article
- UPLC-Orbitrap-MS/MS Combined With Biochemical Analysis to Determine the Growth and Development of Mothers and Fetuses in Different Gestation Periods on Tibetan Sow Model.Frontiers in nutrition · 2022Article
- Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology.Frontiers in pharmacology · 2022Review
- Synthesis and anti-hepatocellular carcinoma activity of aminopyridinol-sorafenib hybrids.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Tryptophan-derived serotonin-kynurenine balance in immune activation and intestinal inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Review
- Saffron Pre-Treatment Promotes Reduction in Tissue Inflammatory Profiles and Alters Microbiome Composition in Experimental Colitis Mice.Molecules (Basel, Switzerland) · 2021Article
- NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology.Antioxidants (Basel, Switzerland) · 2021Review
- Antioxidant Analogue 6-Amino-2,4,5-Trimethylpyridin-3-ol Ameliorates Experimental Colitis in Mice.Digestive diseases and sciences · 2021Article
- Role of platelets and breast cancer stem cells in metastasis.World journal of stem cells · 2020Review
- Potent Inhibitory Effect of BJ-3105, a 6-Alkoxypyridin-3-ol Derivative, on Murine Colitis Is Mediated by Activating AMPK and Inhibiting NOX.International journal of molecular sciences · 2020Article
- Evaluation of serotonin receptors (5HTR2A and 5HTR3A) mRNA expression changes in tumor of breast cancer patients.Medical journal of the Islamic Republic of Iran · 2020Article
- 5-HT serotonin receptors modulate mitogenic signaling and impact tumor cell viability.Molecular and clinical oncology · 2018Article
- BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis.Biological research · 2017Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Hydroxytryptamine (5-HT) induces proliferation of cancer cells and vascular cells. In addition to 5-HT production by several cancer cells including gastrointestinal and breast cancer, a significant level of 5-HT is released from activated platelets in the thrombotic environment of tumors, suggesting that inhibition of 5-HT signaling may constitute a new target for antiangiogenic anticancer drug discovery. In the current study we clearly demonstrate that 5-HT-induced angiogenesis was mediated through the 5-HT1 receptor-linked Gβγ/Src/PI3K pathway, but not through the MAPK/ERK/p38 pathway. In addition, 5-HT induced production of NADPH oxidase (NOX)-derived reactive oxygen species (ROS). In an effort to develop new molecularly targeted anticancer agents against 5-HT action in tumor growth, we demonstrate that BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, significantly inhibited 5-HT-induced angiogenesis. In addition, BJ-1108 induced a significant reduction in the size and weight of excised tumors in breast cancer cell-inoculated CAM assay, showing proportionate suppression of tumor growth along with inhibition of angiogenesis. In human umbilical vein endothelial cells (HUVECs), BJ-1108 significantly suppressed 5-HT-induced ROS generation and phosphorylation of PI3K/Akt but not of Src. Unlike NOX inhibitors, BJ-1108, which showed better antioxidant activity than vitamin C, barely suppressed superoxide anion induced by mevalonate or geranylgeranyl pyrophosphate which directly activates NOX without help from other signaling molecules in HUVECs, implying that the anti-angiogenic action of BJ-1108 was not mediated through direct action on NOX activation, or free radical scavenging activity. In conclusion, BJ-1108 inhibited 5-HT-induced angiogenesis through PI3K/NOX signaling but not through Src, ERK, or p38.
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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.