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image of Dihydromyricetin: A Multitarget Anticancer Agent Exhibiting Cytotoxic and Anti-Angiogenic Activities in Preclinical Models

Abstract

Introduction

Dihydromyricetin (DMY) presents itself as a promising therapeutic candidate due to its inhibitory effects on various receptor tyrosine kinases, prompting an investigation of its structural characteristics, molecular interactions, and biological activity across the FGFR, HER, PDGFR, and VEGFR families.

Methods

Protein sequences and structures for FGFR1/2, HER2/3, PDGFRA/B, and VEGFR1/2 were retrieved from UniProt/PDB. DMY and reference inhibitors were docked to each kinase using AutoDock Vina. Anti-angiogenic activity was measured by HET-CAM assay with vessel metrics quantified IKOSA CAM. MTT determined cytotoxicity (IC) and tumor-selectivity index in 4T1 and L929 cells; data (mean ± SEM) were analyzed by one-way ANOVA with Tukey’s test (p < 0.005).

Results

DMY exhibited docking scores comparable to established inhibitors, achieved over 45 % inhibition of neovascularization in the HET-CAM assay at nanomolar concentrations, displayed a tumor-selectivity index of less than one in 4T1 versus L929 cells (mirroring many clinical chemotherapeutics), and, notably, coadministration with doxorubicin reduced cardiotoxicity markers.

Discussion

The high-affinity, multi-kinase binding profile and significant anti-angiogenic efficacy underscore DMY’s multifunctional potential, while its tumor-selectivity index aligns with accepted therapeutic risk–benefit balances and its cardioprotective effect suggests a way to mitigate anthracycline toxicity.

Conclusion

These findings indicate that DMY is a multifunctional agent exhibiting both anti-angiogenic and cytotoxic properties, warranting further preclinical and clinical investigation.

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2026-01-08
2026-01-31

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Dihydromyricetin: A Multitarget Anticancer Agent Exhibiting Cytotoxic and Anti-Angiogenic Activities in Preclinical Models
Bentham Science Publishers ; https://doi.org/10.2174/0115680266398105251020100300
/content/journals/ctmc/10.2174/0115680266398105251020100300
/content/journals/ctmc/10.2174/0115680266398105251020100300
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  • Article Type:     Research Article
Keywords: HET-CAM ; Antitumoral ; Molecular Docking ; Angiogenesis ; Flavonoids ; Dihydromyricetin

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