Elevated IL-1β expression induces invasiveness of triple negative breast cancer cells and is suppressed by zerumbone

Aberrant interleukin-1 beta (IL-1 beta) expression is associated with cancer development, metastasis, and poor prognosis. Here, we have investigated the regulatory mechanism of IL-1 beta expression, and the inhibitory effect of zerumbone (ZER) on IL-1 beta expression and IL-1 beta-induced signatures, including cell invasion and signaling activation in triple negative breast cancer (TNBC) cells. The basal IL-1 beta and cell invasiveness levels were significantly higher in TNBC cells, compared with non-TNBC cells. The invasiveness of TNBC cells was also increased following IL-1 beta treatment. In contrast, the invasiveness of TNBC cells was decreased following IL-1 receptor antagonist (IL-1RA) treatment. Additionally, the basal IL-1b level and the invasiveness of TNBC cells were decreased by Bay11-7085. In contrast, overexpression of NF-kappa B (p65) caused an increase in IL-1 beta expression in TNBC cells. Our results showed that treatment with ZER decreased the basal IL-1 beta expression level, and the phosphorylation level of NF-kappa B, in TNBC cells. Furthermore, we found that ZER completely suppressed IL-1 beta-induced NF-kappa B phosphorylation, but did not suppress IL-1 beta-induced Akt phosphorylation, in TNBC cells. Our results also demonstrate that IL-1 beta-induced cell invasion is suppressed by ZER in TNBC cells. Taken together, we demonstrated that IL-1 beta expression is regulated by the NF-kappa B-dependent pathway, and that elevated IL-1 beta is directly influencing the invasiveness of TNBC cells. ZER down-regulates IL-1 beta expression through the inhibition of NF-kappa B activity, and then suppresses cell invasiveness of TNBC. (C) 2016 Published by Elsevier Ireland Ltd.