Ginkgolide C promotes apoptosis and abrogates metastasis of colorectal carcinoma cells by targeting Wnt/β-catenin signaling pathway.

Abstract

Ginkgolide C (GGC), isolated from Ginkbiloba, has been reported to display various pharmacological actions, although, anti-cancer effect of GGC has been poorly understood till now. This study aimed to investigate whether GGC can exhibit anti-neoplastic effects against colon cancer cells and explore underlying mechanism. The Wnt/β-catenin signaling can regulate cell proliferation, survival, metastasis, and migration. Wnt/β-catenin signaling pathway plays important role in colorectal cancer (CRC) and acts as a potential therapeutic target. Abnormal activation of this signaling cascades has been reported in colon CRC. We found that GGC down-regulated Wnt/β-catenin signaling cascade. GGC inhibited the expression of Wnt3a, β-catenin, and β-catenin down-stream signals (Axin-1, p-GSK3β, and β-TrCP). Also, GGC suppressed the expression of Wnt/β-catenin pathway target genes including c-myc, cyclin D1, and survivin. Additionally, GGC induced apoptosis and suppressed cell proliferation, invasion, and migration. GGC down-regulated the expressions of matrix metalloproteinase (MMP)-9 and MMP-2 proteins. Moreover, silencing of β-catenin by small interfering RNA (siRNA) enhanced the GGC-induced apoptosis and inhibitory action of GGC on invasion. Overall, our results indicate that GGC can reduce proliferation and promote apoptosis in colon cancer cells through inhibition of the Wnt/β-catenin signaling pathway. Thus, GGC can serve as a potent therapeutic agent for management of colon cancer as a novel wnt signaling inhibitor.

• Authors: Min Hee Yang, In Jin Ha, Seok-Geun Lee, Junhee Lee, Jae-Young Um, Kwang Seok Ahn
• Journal: IUBMB life (IUBMB Life) Vol. 73 Issue 10 Pg. 1222-1234 (10 2021) ISSN: 1521-6551 [Electronic] England
• PMID: 34273236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 International Union of Biochemistry and Molecular Biology.

Chemical References

• Antineoplastic Agents
• CTNNB1 protein, human
• Ginkgolides
• Lactones
• beta Catenin
• ginkgolide C

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects)
• Cell Survival
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Ginkgolides (pharmacology)
• Humans
• Lactones (pharmacology)
• Wnt Signaling Pathway (drug effects, genetics)
• beta Catenin (genetics, metabolism)