Background: Curcumin, a well-studied component in turmeric, exhibits potent antitumor effects in colorectal cancer. Previous studies showed that turmerones raised the accumulation of curcumin inside colonic cells, and curcumin present in turmeric ethanolic extract had enhanced anti-tumor activities in mice. Metastasis accounts for more than 90% colorectal cancer deaths. However, the anti-metastatic effect of turmeric extract on colorectal cancer is still unknown.
Methods: In the present study, colony formation, scratch, transwell and Western blot were used to assess colony formation, motility, migration and underlying mechanisms in vitro, respectively. Anti-tumor and anti-metastatic effects in vivo were investigated using an orthotopic xenograft model.
Results: Turmeric extract exhibited cytotoxic effect, inhibited colony formation, decreased cell motility, migration and epithelial-mesenchymal transitions through regulating multiple pathways including cofilin, FAK/p-Src, AKT, Erk and STAT3 signaling pathways in murine colorectal cancer cells. Furthermore, turmeric extract at 200 mg/kg could decrease colon tumor burden and inhibit liver and lung metastasis in vivo. Treatment of turmeric extract enhanced immunity through T cell stimulation, changed tumor microenvironment, exerted anti-metastatic effects which were shown for the first time in pre-clinical colorectal cancer models. The decrease of immunity after FOLFOX treatment was also firstly demonstrated in mouse model.
Conclusions: Turmeric extract was demonstrated for the first time for its anti-tumor and anti-metastatic effects in both colorectal cancer cells and orthotopic mouse model through regulation of multiple targets. These findings strongly suggested the promising use of turmeric extract as chemopreventive or chemotherapeutic agent for colorectal cancer patients with metastasis.
Keywords: Colorectal cancer; Curcumin; Metastasis; Orthotopic mouse model; Tumor microenvironment; Turmeric extract.
Copyright © 2018. Published by Elsevier GmbH.