Anti-neoplastic Effect of Ginkgolide C through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma Cells

Abstract

Ginkgolide C (GGC) derived from Ginkgo biloba, has been reported to exhibit various biological functions. However, the anti-neoplastic effect of GGC and its mechanisms in liver cancer have not been studied previously. Hepatocyte growth factor (HGF)/c-mesenchymal–epithelial transition receptor (c-Met) pathway can regulate tumor growth and metastasis in hepatocellular carcinoma (HCC) cells. This study aimed to evaluate the anti-neoplastic effect of GGC against HCC cells and we observed that GGC inhibited HGF-induced c-Met and c-Met downstream oncogenic pathways, such as PI3K/Akt/mTOR and MEK/ERK. In addition, GGC also suppressed the proliferation of expression of diverse tumorigenic proteins (Bcl-2, Bcl-xL, Survivin, IAP-1, IAP-2, Cyclin D1, and COX-2) and induced apoptosis. Interestingly, the silencing of c-Met by small interfering RNA (siRNA) mitigated c-Met expression and enhanced GGC-induced apoptosis. Moreover, it was noted that GGC also significantly reduced the invasion and migration of HCC cells. Overall, the data clearly demonstrate that GGC exerts its anti-neoplastic activity through modulating c-Met phosphorylation and may be used as an effective therapy against HCC.

Identification of hepatoprotective traditional Chinese medicines based on the structure–activity relationship, molecular network, and machine learning techniques

“…Interestingly, the hepatoprotective “TCM-ingredient” network discovered 44 hepatoprotective ingredients for Chai Hu. In fact, systematical literature retrieval only led to 2 ( Sugawara and Igarashi, 2009 ), 3 ( Lee et al, 2017 ; Lee et al, 2018 ), and 6 ( Wei et al, 2014 ; Yang M. H. et al, 2020 ; Yang Y. et al, 2020 ; Sarkar et al, 2020 ) hepatoprotective ingredients for Ju Hua, Sang Ye, and Yin Xing Ye. In contrast, the “TCM-ingredient” network discovered 34, 35, and 34 hepatoprotective ingredients for the corresponding TCMs, respectively.…”

“…Of note, ginkgolide C, a hepatoprotective ingredient derived from Yin Xing Ye, was not identified successfully by the hepatoprotective “TCM-ingredient” network. Literature searches found that a total of two studies reported the hepatoprotective activity of ginkgolide C ( Huang W. C. et al, 2018 ; Yang M. H. et al, 2020 ). However, there was no TCM-related vocabulary that existed in the abstracts or titles of these two studies.…”

Development of a Novel CTCs/CTMs Related Prognostic Signature for Hepatocellular Carcinoma

“…Ginkgolide A is a platelet-activating factor antagonist extracted from Ginkgo biloba, and a literature review mentioned its many biological effects, such as anti-in ammatory, anti-cancer, anti-anxiety, anti-atherosclerotic, neurological, and hepatoprotective effects (42). However, a recent report highlighted that another derivative from Ginkgo biloba, ginkgolide C, exhibited its anti-hepatocarcinoma effection by modulating c-Met phosphorylation (43). In conclusion, our analysis is undoubtedly helpful, but its application in future studies is necessary.…”

Albendazole Exhibits Anti-Neoplastic Actions against Gastric Cancer Cells by Affecting STAT3 and STAT5 Activation by Pleiotropic Mechanism(s)

“…Then, cells were resuspended in 1× PBS containing RNase A for 1 h at 37 °C and stained with propidium iodide. Cells were analyzed by BD Accuri™ C6 Plus Flow Cytometer (BD Biosciences, Becton-Dickinson) equipped with the BD Accuri C6 Plus software [ 55 ].…”