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

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. [ABSTRACT FROM AUTHOR]