Para-Coumaric Acid Suppresses Vascular Endothelial Growth Factor-Induced DLL4-NOTCH1 Signaling, Tumor Angiogenesis, and Tumor Growth

하승환, Jihye You, So Hee Bae, Hyoung-Geun Kim, Nam‐In Baek, Ji-Hak Jeong, Jeong Ah Kim, You Mie Lee

PULSE · 2026-yil

Annotatsiya

Introduction: DLL4-NOTCH1 signaling mediates juxtacrine communication between tip- and stalk-like endothelial cells during vascular sprouting, contributing to complementary aspects of endothelial function. Thus, simultaneous modulation of DLL4 and NOTCH1 may provide a strategy to broadly interfere with the endothelial functions involved in tumor angiogenesis. Accordingly, this study aimed to identify a novel natural compound capable of modulating DLL4-NOTCH1-mediated endothelial communication and to investigate how such modulation influences tumor angiogenesis and growth. Methods: We screened 66 natural compounds to identify those that suppress DLL4 and NOTCH1 signaling in endothelial cells. Using a dual-reporter system that combines a DLL4 promoter-driven reporter and a CSL luciferase reporter, we simultaneously assessed ligand-associated activity and downstream transcriptional output of the DLL4-NOTCH1 axis. We confirmed VEGF-induced target gene expression via Western blotting and quantitative real-time polymerase chain reaction. We further performed in vitro angiogenesis assays and in vivo Lewis lung carcinoma (LLC) allograft tumor experiments. Results: Among the 66 screened natural compounds, para-coumaric acid (p-CA) dose-dependently suppressed DLL4 transcription and NOTCH1 signaling activity in endothelial cells, with IC50 values of 4.57 and 8.34 µm, respectively. Furthermore, p-CA significantly suppressed VEGF-induced endothelial cell proliferation, migration, and tube formation. In the LLC allograft model, p-CA treatment suppressed tumor growth and vascular density, increased pericyte coverage, reduced tumor hypoxia, and enhanced CD3+ T-cell infiltration and tumor cell apoptosis. Conclusion: In summary, p-CA is a natural compound that functionally suppresses VEGF-driven DLL4-NOTCH1 signaling in endothelial cells, exhibiting strong anti-angiogenic effects and promoting functional vascular normalization, resulting in marked tumor suppression and enhanced antitumor immunity in vivo. These findings suggest that p-CA warrants further investigation as an anti-angiogenic compound for cancer therapy.

Maqola ma’lumotlari
Mualliflar하승환, Jihye You, So Hee Bae, Hyoung-Geun Kim, Nam‐In Baek, Ji-Hak Jeong, Jeong Ah Kim, You Mie Lee
JurnalPULSE
NashriyotPROFI университетининг
ISSN2074-1855, 2235-8668
Nashr sanasi2026-06-19
Jild14
Son1
Betlar105-118
TilIngliz
Ilmiy sohaPsixologiya
DOI10.1159/000553024
Indeksga qo‘shilgan2026-09-02

DOI: 10.1159/000553024 · Maqolaning asl sahifasi · PDF

Ilmiy soha

Psixologiya

Iqtibos keltirish

APA하승환, Jihye You, So Hee Bae, Hyoung-Geun Kim, Nam‐In Baek, Ji-Hak Jeong, Jeong Ah Kim, & You Mie Lee (2026). Para-Coumaric Acid Suppresses Vascular Endothelial Growth Factor-Induced DLL4-NOTCH1 Signaling, Tumor Angiogenesis, and Tumor Growth. PULSE, 14(1), 105-118. https://doi.org/10.1159/000553024
GOST (OAK)하승환 va b. Para-Coumaric Acid Suppresses Vascular Endothelial Growth Factor-Induced DLL4-NOTCH1 Signaling, Tumor Angiogenesis, and Tumor Growth // PULSE. – 2026. – T. 14, № 1. – P. 105-118. – DOI: 10.1159/000553024.
MLA하승환, Jihye You, So Hee Bae, Hyoung-Geun Kim, Nam‐In Baek, Ji-Hak Jeong, Jeong Ah Kim, and You Mie Lee. “Para-Coumaric Acid Suppresses Vascular Endothelial Growth Factor-Induced DLL4-NOTCH1 Signaling, Tumor Angiogenesis, and Tumor Growth.” PULSE, 14(1), 105-118, 2026. https://doi.org/10.1159/000553024
Chicago하승환, Jihye You, So Hee Bae, Hyoung-Geun Kim, Nam‐In Baek, Ji-Hak Jeong, Jeong Ah Kim, and You Mie Lee. “Para-Coumaric Acid Suppresses Vascular Endothelial Growth Factor-Induced DLL4-NOTCH1 Signaling, Tumor Angiogenesis, and Tumor Growth.” PULSE, 14(1), 105-118 (2026). https://doi.org/10.1159/000553024
Harvard하승환, Jihye You, So Hee Bae, Hyoung-Geun Kim, Nam‐In Baek, Ji-Hak Jeong, Jeong Ah Kim, and You Mie Lee (2026) ‘Para-Coumaric Acid Suppresses Vascular Endothelial Growth Factor-Induced DLL4-NOTCH1 Signaling, Tumor Angiogenesis, and Tumor Growth’, PULSE, 14(1), 105-118. https://doi.org/10.1159/000553024
BibTeX
@article{article2026,
  title = {Para-Coumaric Acid Suppresses Vascular Endothelial Growth Factor-Induced DLL4-NOTCH1 Signaling, Tumor Angiogenesis, and Tumor Growth},
  author = {하승환 and Jihye You and So Hee Bae and Hyoung-Geun Kim and Nam‐In Baek and Ji-Hak Jeong and Jeong Ah Kim and You Mie Lee},
  journal = {PULSE},
  year = {2026},
  volume = {14},
  number = {1},
  pages = {105-118},
  doi = {10.1159/000553024},
  url = {https://doi.org/10.1159/000553024}
}

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