title: Elevated IL-1β expression induces invasiveness of triple negative breast cancer cells and is suppressed by zerumbone.
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.
authors: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea.
authors: Myeongjin
authors: M
authors: Jeon
authors: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea.
authors: Jeonghun
authors: J
authors: Han
authors: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea.
authors: Seok Jin
authors: SJ
authors: Nam
authors: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea. Electronic address: paojlus@hanmail.net.
authors: Jeong Eon
authors: JE
authors: Lee
authors: Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea. Electronic address: sangmin3005.kim@samsung.com.
authors: Sangmin
authors: S
authors: Kim
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D012717:Sesquiterpenes; C403304:zerumbone
keywords: Cell invasion; IL-1β; NF-κB; Triple-negative breast cancer; Zerumbone