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.