Elevated IL-1β expression induces invasiveness of triple negative breast cancer cells and is suppressed by zerumbone. (25th October 2016)

• Record Type: Journal Article
• Authors: Jeon, Myeongjin; Han, Jeonghun; Nam, Seok Jin; Lee, Jeong Eon; Kim, Sangmin
• Is Part Of: Chemico-biological interactions. Volume 258(2016)
• Page Start: 126
• Page End: 133
• Publication Date: 2016-10-25
• Subjects: Zerumbone -- Triple-negative breast cancer -- IL-1β -- Cell invasion -- NF-κB; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2016.08.021
• Languages: English
• ISSNs: 0009-2797

Abstract

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