University of Kansas Medical Center, Kansas City, KS, USA.
Integr Cancer Ther. 2023 Jan-Dec;22:15347354221134513. doi: 10.1177/15347354221134513.
The popular dietary supplements of (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.
（银杏）产品作为一种广受欢迎的膳食补充剂，在多项细胞和动物研究中被报道具有抗癌活性，但这些益处尚未通过临床试验得到证实。其作用机制尚不清楚，这给研究银杏对癌症患者的具体益处形成了障碍，尤其是当与其他疗法结合使用时。在这里，我们报道了一种银杏金叶提取物（GGLE）抑制黑素瘤细胞侵袭和血管生成的新机制。GGLE 并没有通过直接细胞毒性抑制黑素瘤细胞。相反，GGLE 显著抑制了常氧和缺氧条件下黑素瘤细胞中的总核糖核酸酶活性。缺氧诱导了核糖核酸酶血管生成素的两倍表达，而 GGLE 处理以剂量依赖的方式显著抑制了这种诱导。由于血管生成素的抑制，GGLE 以剂量依赖的方式抑制了黑素瘤细胞的迁移和侵袭。黑素瘤细胞培养的条件培养基足以在人内皮细胞中诱导体外血管生成，而 GGLE 处理的黑素瘤细胞的条件培养基则显著抑制了这种血管生成活性。这伴随着 GGLE 处理的黑素瘤细胞条件培养基中血管生成素浓度的明显降低。我们得出结论，与直接细胞毒性相反，GGLE 抑制了黑素瘤细胞中血管生成素的合成和分泌，从而抑制了肿瘤细胞的侵袭和肿瘤诱导的血管生成。这一新机制为研究 GGLE 影响肿瘤微环境打开了大门，并需要进一步在体内进行研究和验证。
