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.