PMID- 33428135 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20210924 IS - 2523-899X (Electronic) IS - 2523-899X (Linking) VI - 40 IP - 6 DP - 2020 Dec TI - Promising Effects of Zerumbone on the Regulation of Tumor-promoting Cytokines Induced by TNF-alpha-activated Fibroblasts. PG - 1075-1084 LID - 10.1007/s11596-020-2289-7 [doi] AB - Inflammation plays an important role in the development of several cancers. Inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), are associated with the induction of inflammation. Chronic inflammation contributes to the progression of cancer through several mechanisms, including increased cytokine production and activation of transcription factors, such as nuclear factor-kappaB (NF-kappaB). Zerumbone (ZER), a component of subtropical ginger (Zingiber zerumbet Smith), seems to have anti-inflammatory, anti-cancer, and antioxidant activities. In this study, we aimed to explore the protective function and mechanisms of ZER against TNF-alpha-induced cancer-promoting cytokines. We found that the viability of stimulated human fibroblast cell lines was reduced after treatment with ZER (IC(50)=18 micromol/L), compared to un-stimulated fibroblasts (IC(50)=40 micromol/L). Besides, ZER inhibited mRNA expression and protein secretion of transforming growth factor-beta (TGF-beta), interleukin-33 (IL-33), monocyte chemoattractant protein-1 (MCP-1), and stromal cell-derived factor 1 (SDF-1), which were produced by TNF-alpha-induced fibroblasts, as measured by quantitative real time-PCR (qRT-PCR) and ELISA assays. The mRNA expression levels of TGF-beta, IL-33, SDF-1, and MCP-1 showed 8, 5, 2.5, and 4-fold reductions, respectively. Moreover, secretion of TGF-beta, IL-33, SDF-1, and MCP-1 was reduced to 3.65+/-0.34 ng/mL, 6.3+/-0.26, 1703.6+/-295.2, and 5.02+/-0.18 pg/mL, respectively, compared to the untreated group. In addition, the conditioned media (CM) of TNF-alpha-stimulated fibroblasts increased the NF-kappaB expression in colorectal cancer cell lines (HCT-116 and Sw48), while in the vicinity of ZER, the expression of NF-kappaB was reversed. Considering the significant effects of ZER, this component can be used as an appropriate alternative herbal treatment for cancer-related chronic inflammation. FAU - Radaei, Zahra AU - Radaei Z AD - Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran. FAU - Zamani, Alireza AU - Zamani A AD - Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran. FAU - Najafi, Rezvan AU - Najafi R AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran. FAU - Saidijam, Massoud AU - Saidijam M AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran. FAU - Jalilian, Farid Azizi AU - Jalilian FA AD - Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran. FAU - Ezati, Razieh AU - Ezati R AD - Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, 14965, Iran. FAU - Solgi, Ghasem AU - Solgi G AD - Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran. FAU - Amini, Razieh AU - Amini R AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran. aminra14@gmail.com. LA - eng PT - Journal Article DEP - 20210111 PL - China TA - Curr Med Sci JT - Current medical science JID - 101729993 RN - 0 (Anti-Inflammatory Agents) RN - 0 (CCL2 protein, human) RN - 0 (CXCL12 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL12) RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (IL33 protein, human) RN - 0 (Interleukin-33) RN - 0 (NF-kappa B) RN - 0 (Sesquiterpenes) RN - 0 (Transforming Growth Factor beta) RN - 0 (Tumor Necrosis Factor-alpha) RN - 471-05-6 (zerumbone) SB - IM MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Culture Techniques MH - Cell Line MH - Cell Survival/drug effects MH - Chemokine CCL2/genetics/metabolism MH - Chemokine CXCL12/genetics/metabolism MH - Culture Media, Conditioned/chemistry MH - Cytokines/*genetics/*metabolism MH - Fibroblasts/*cytology/drug effects/immunology MH - Gene Expression Regulation, Neoplastic/drug effects MH - HCT116 Cells MH - Humans MH - Interleukin-33/genetics/metabolism MH - NF-kappa B/genetics/metabolism MH - Sesquiterpenes/*pharmacology MH - Transforming Growth Factor beta/genetics/metabolism MH - Tumor Necrosis Factor-alpha/*adverse effects OTO - NOTNLM OT - activated fibroblasts OT - inflammation OT - nuclear factor-alphaB (NF-alphaB) OT - tumor necrosis factor-alpha (TNF-alpha) OT - zerumbone EDAT- 2021/01/12 06:00 MHDA- 2021/09/25 06:00 CRDT- 2021/01/11 12:21 PHST- 2019/05/23 00:00 [received] PHST- 2019/11/26 00:00 [accepted] PHST- 2021/01/11 12:21 [entrez] PHST- 2021/01/12 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] AID - 10.1007/s11596-020-2289-7 [pii] AID - 10.1007/s11596-020-2289-7 [doi] PST - ppublish SO - Curr Med Sci. 2020 Dec;40(6):1075-1084. doi: 10.1007/s11596-020-2289-7. Epub 2021 Jan 11.