Inhibitory effect of quercetin on colorectal lung metastasis through inducing apoptosis, and suppression of metastatic ability

• Published in: Phytomedicine (Stuttgart) 2016-12, Vol.23 (13), p.1680-1690
• Main Authors: Kee, Ji-Ye, Han, Yo-Han, Kim, Dae-Seung, Mun, Jeong-Geon, Park, Jinbong, Jeong, Mi-Young, Um, Jae-Young, Hong, Seung-Heon
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic - drug effects; HT29 Cells - drug effects; Humans; Lung metastasis; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Matrix Metalloproteinases - metabolism; Mice, Inbred BALB C; Mitogen-activated protein kinases; Mitogen-Activated Protein Kinases - metabolism; Quercetin; Quercetin - pharmacology
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2016.09.011

Quercetin is a major dietary flavonoid found in a various fruits, vegetables, and grains. Although the inhibitory effects of quercetin have previously been observed in several types of cancer cells, the anti-metastatic effect of quercetin on colorectal metastasis has not been determined. This study investigated whether quercetin exhibits inhibitory effect on colorectal lung metastasis. The effects of quercetin on cell viability, mitogen-activated protein kinases (MAPKs) activation, migration, invasion, epithelial-mesenchymal transition (EMT) and lung metastasis were investigated. We investigated the effect of quercetin on metastatic colon cancer cells using WST assay, Annexin V assay, real-time RT-PCR, western blot analysis and gelatin zymography. The anti-metastatic effect of quercetin in vivo was confirmed in a colorectal lung metastasis model. Quercetin inhibited the cell viability of colon 26 (CT26) and colon 38 (MC38) cells and induced apoptosis through the MAPKs pathway in CT26 cells. Expression of EMT markers, such as E-, N-cadherin, β-catenin, and snail, were regulated by non-toxic concentrations of quercetin. Moreover, the migration and invasion abilities of CT26 cells were inhibited by quercetin through expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) regulation. Quercetin markedly decreased lung metastasis of CT26 cells in an experimental in vivo metastasis model. In conclusion, this study demonstrates for the first time that quercetin can inhibit the survival and metastatic ability of CT26 cells, and it can subsequently suppress colorectal lung metastasis in the mouse model. These results indicate that quercetin may be a potent therapeutic agent for the treatment of metastatic colorectal cancer. [Display omitted]