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Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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In Vivo Imaging and Quantitation of the Host Angiogenic Response in Zebrafish Tumor Xenografts
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Canthin-6-One Inhibits Developmental and Tumour-Associated Angiogenesis in Zebrafish.

Mei Fong Ng1, Juliana Da Silva Viana2,3, Pei Jean Tan1

  • 1Cancer Research Malaysia, Subang Jaya 47500, Selangor, Malaysia.

Pharmaceuticals (Basel, Switzerland)
|January 23, 2024
PubMed
Summary
This summary is machine-generated.

Canthin-6-one, a natural compound, inhibits tumour angiogenesis by targeting endothelial cell proliferation independently of the VEGFA/VEGFR2 pathway. This discovery offers a potential new anti-cancer therapeutic strategy.

Keywords:
angiogenesiscancercanthin-6-onenatural productzebrafish

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Area of Science:

  • Oncology
  • Pharmacology
  • Developmental Biology

Background:

  • Tumour-associated angiogenesis is crucial for cancer growth and metastasis.
  • Current anti-angiogenic drugs targeting VEGFA/VEGFR2 have limitations due to resistance and increased tumour aggressiveness.
  • Novel anti-angiogenic strategies independent of the VEGFA/VEGFR2 pathway are needed.

Purpose of the Study:

  • To screen for novel anti-angiogenic molecules from natural products using a zebrafish model.
  • To investigate the mechanism of action of identified compounds.
  • To evaluate the therapeutic potential of identified compounds in cancer models.

Main Methods:

  • Zebrafish model for high-throughput screening of natural product library.
  • In vitro assays using human umbilical vein endothelial cells (HUVECs).
  • Zebrafish xenograft model with B16F10 melanoma cells.
  • Western blot analysis for VEGFA/VEGFR2 pathway activation.

Main Results:

  • Canthin-6-one, an indole alkaloid, was identified as a novel anti-angiogenic compound.
  • Canthin-6-one inhibited zebrafish intersegmental vessel (ISV) development and endothelial cell proliferation.
  • Canthin-6-one's mechanism is independent of the VEGFA/VEGFR2 pathway.
  • Canthin-6-one impaired tumour angiogenesis in a zebrafish xenograft model and synergized with sunitinib malate.

Conclusions:

  • Canthin-6-one exhibits potent anti-angiogenic properties in both developmental and pathological settings.
  • Canthin-6-one represents a promising candidate for novel anti-cancer drug development.
  • Targeting angiogenesis independently of the VEGFA/VEGFR2 pathway offers a viable strategy to overcome drug resistance.