Zerumbone Suppresses IL-1 beta-induced Cell Migration and Invasion by Inhibiting IL-8 and MMP-3 Expression in Human Triple-negative Breast Cancer Cells

Abstract

Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)-1 is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1-induced cell migration and invasion in breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8 and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL-8 and MMP-3 expression were significantly increased by IL-1 treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1-induced cell migration and invasion by inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple-negative breast cancer patients. Copyright (c) 2014 John Wiley & Sons, Ltd.