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.

• Authors: Min Hee Yang, Seung Ho Baek, Jae-Young Um, Kwang Seok Ahn
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 21 (Nov 05 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33167504 (Publication Type: Journal Article)

Chemical References

• Ginkgolides
• Lactones
• ginkgolide C
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met

Topics

• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Ginkgolides (metabolism, pharmacology)
• Hep G2 Cells
• Hepatocyte Growth Factor (metabolism)
• Humans
• Lactones (metabolism, pharmacology)
• Liver Neoplasms (drug therapy, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-met (metabolism)
• Signal Transduction (drug effects)