Ginkgolic acid suppresses the invasion of HepG2 cells via downregulation of HGF/c‑Met signaling

Abstract

Liver cancer is one of the most devastating types of cancer worldwide. Despite years of improvements in treatment, the prognosis of patients with this type of malignancy remains poor due to frequent recurrence and metastasis after surgical resection. Ginkgolic acid (GA) is a botanical drug extracted from the seed coat of Ginkgo biloba L. that possesses a wide range of bioactive properties. However, to the best of our knowledge, whether GA can inhibit the invasion of liver cancer cells and the underlying mechanisms remains unknown. The aim of the present study was to investigate the effects of GA on the migration and invasion abilities of liver cancer cells and the underlying molecular mechanism. The results revealed that GA suppressed the migration and invasion abilities of HepG2 cells. In addition, GA treatment inhibited the expression of invasion-related molecules (MMP-2 and MMP-9) and prevented the epithelial-mesenchymal transition (EMT) of HepG2 cells. Further experiments revealed that GA-reduced hepatocyte growth factor (HGF) production and suppressed c-Met phosphorylation may be the underlying mechanisms. Exogenous recombinant HGF supplementation improved the cell invasion ability impaired by GA. Moreover, the in vivo experiment revealed that GA inhibited the tumor growth of liver cancer and prevented EMT. Collectively, these data indicated that GA effectively suppressed the invasion and EMT of HepG2 cells via downregulation of HGF/c-Met signaling, thus GA may serve as a novel chemotherapeutic agent for the

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

“…Collectively, the results of the present study indicated that GA suppressed the development of RCC. These results were consistent with previous studies demonstrating that GA plays an inhibitory biological role in cancer (12)(13)(14)(15)25). However, the biological effect of GA on RCC was observed at high concentrations of GA in vitro and it is uncertain whether this concentration would be possible in vivo.…”

“…Extracts from natural plants are becoming an increasingly popular strategy to identify novel antitumor compounds (23,24). Recently, several studies have reported that GA displays promising antitumor activities (12)(13)(14)(15). Therefore, identification of the regulatory mechanism of GA in tumorigenesis would provide valuable insight for the treatment of malignancies.…”

“…GA suppresses tumor growth and invasion via various signaling pathways, including the hepatocyte growth factor/c-Met signaling pathway in hepatocellular carcinoma (12), the protein kinase AMP-activated catalytic subunit α2 signaling pathway in colon cancer (13), the NF-κB signaling pathway in breast cancer (14) and the PI3K/Akt/mTOR signaling pathway in lung cancer (15). A number of studies have reported that, in addition to inducing cell cycle arrest, GA also increases apoptosis in colon cancer and hepatocellular carcinoma (26,27).…”

“…Network pharmacology provides a strategy to investigate complex mechanisms of drug action and to identify potential drug targets (28). In a network pharmacology system, therapy response can be taken into account based on the robustness of complex disease networks in dealing with node attacks (node linking degree) due to inherent diversity and redundant compensation signaling pathways (12,19). The result of network pharmacology is a highly resilient network system with topological interaction (19,29).…”

“…GA has been reported to display a wide range of bioactive properties, including antimicrobial, antivirus and molluscicidal activities (11). Accumulating evidence has demonstrated that several monomer structures of GA (C13:0, C15:0 and C17:1) exert antitumor activity in a number of human malignancies, including hepatocellular carcinoma as well as colon, breast and lung cancer (12)(13)(14)(15). However, to the best of our knowledge, no previous study has been conducted to investigate the pharmacological effect of GA in RCC.…”