interleukin-8 and zerumbone

Topics: Animals; Anti-Bacterial Agents; Bacterial Toxins; Bacteroides fragilis; Bacteroides Infections; Cadherins; Colitis; Colon; Epithelial Cells; HT29 Cells; Humans; Interleukin-17; Interleukin-8; Metalloendopeptidases; Mice; Mice, Inbred C57BL; NF-kappa B; Nitric Oxide Synthase Type II; Sesquiterpenes; Tumor Necrosis Factor-alpha

Because angiogenesis is essential for tumor growth and metastasis, the development of antiangiogenic agents is an urgent issue in cancer treatment. Zerumbone, a component of subtropical ginger, has been shown to exhibit anticancer activities in various cancer cells; however, little is known about its biological mechanisms against angiogenesis in pancreatic cancer (PaCa). Here, we evaluated the effects of zerumbone on PaCa angiogenesis.. The cytotoxicity of zerumbone in PaCa was measured using premix WST-1 cell proliferation assays. The influence of zerumbone on the angiogenic factors vascular endothelial growth factor and interleukin 8 was measured using the reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays. Changes in nuclear factor-κB (NF-κB) activities were measured using NF-κB transcription factor assays. We also examined the effects of zerumbone on PaCa-induced angiogenesis using angiogenesis assays.. Zerumbone inhibited mRNA expression and protein secretion of angiogenic factors and NF-κB activity. Tube formation in human umbilical vein endothelial cells was enhanced by coculture with PaCa cells, and these enhancements were significantly inhibited by zerumbone treatment.. Zerumbone blocked the PaCa-associated angiogenesis through the inhibition of NF-κB and NF-κB-dependent proangiogenic gene products.

Topics: Cell Line; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Coculture Techniques; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Neoplastic; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-8; Neovascularization, Pathologic; Neovascularization, Physiologic; NF-kappa B; Pancreatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Sesquiterpenes; Vascular Endothelial Growth Factor A

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)-1β is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1β-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1β-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-1β treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1β-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1β-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1β-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.

Topics: Cell Line, Tumor; Cell Movement; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-1beta; Interleukin-8; Matrix Metalloproteinase 3; Neoplasm Invasiveness; Sesquiterpenes; Triple Negative Breast Neoplasms