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Ginkgo biloba Golden Leaf Extract (GGLE) Inhibits Melanoma Cell Invasion and Angiogenesis Through Inhibition of Angiogenin.

Abstract
The popular dietary supplements of Ginkgo biloba (Ginkgo) products have been reported to have anti-cancer activities in multiple cellular and animal studies, with the benefits yet to be proven with clinical trials. The mechanisms of action are not clear, forming a barrier to investigation in Gingko-specific benefits to cancer patients, especially when combined with other therapies. Here we reported on the discovery of a novel mechanism by which a Ginkgo golden leaf extract (GGLE) inhibited melanoma cell invasion and angiogenesis. GGLE did not inhibit melanoma cells via direct cytotoxicity. Instead, GGLE significantly inhibited total RNase activities in melanoma cells under both normoxia and hypoxia conditions. The RNase angiogenin was induced twofolds by hypoxia, and the induction was significantly suppressed by GGLE treatment in a dose dependent manner. As a result of angiogenin inhibition, GGLE inhibited melanoma cell migration and invasion in a dose dependent manner. Conditioned media from melanoma cell culture sufficiently induced in vitro angiogenesis in human endothelial cells, whereas the conditioned media of GGLE-treated melanoma cells significantly inhibited this angiogenetic activity. This was accompanied with markedly reduced angiogenin concentrations in the GGLE-treated melanoma cell conditioned media. We concluded that, instead of direct cytotoxicity, GGLE inhibited angiogenin synthesis and secretion by melanoma cells, resulting in inhibition of tumor cell invasion and tumor-induced angiogenesis. This new mechanism opens the door for investigation in GGLE influencing tumor microenvironment, and warrants further investigation and validation in vivo.
AuthorsPing Chen, Tao Wang, Qi Chen
JournalIntegrative cancer therapies (Integr Cancer Ther) 2023 Jan-Dec Vol. 22 Pg. 15347354221134513 ISSN: 1552-695X [Electronic] United States
PMID36859800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • angiogenin
  • Culture Media, Conditioned
  • Plant Extracts
  • Ribonucleases
Topics
  • Humans
  • Culture Media, Conditioned
  • Endothelial Cells
  • Ginkgo biloba
  • Melanoma
  • Plant Extracts (pharmacology)
  • Ribonucleases
  • Tumor Microenvironment

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