Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran.
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, 65178, Iran.
Curr Med Sci. 2020 Dec;40(6):1075-1084. doi: 10.1007/s11596-020-2289-7. Epub 2021 Jan 11.
Inflammation plays an important role in the development of several cancers. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), 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-κB (NF-κB). 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-α-induced cancer-promoting cytokines. We found that the viability of stimulated human fibroblast cell lines was reduced after treatment with ZER (IC=18 µmol/L), compared to un-stimulated fibroblasts (IC=40 µmol/L). Besides, ZER inhibited mRNA expression and protein secretion of transforming growth factor-β (TGF-β), interleukin-33 (IL-33), monocyte chemoattractant protein-1 (MCP-1), and stromal cell-derived factor 1 (SDF-1), which were produced by TNF-α-induced fibroblasts, as measured by quantitative real time-PCR (qRT-PCR) and ELISA assays. The mRNA expression levels of TGF-β, IL-33, SDF-1, and MCP-1 showed 8, 5, 2.5, and 4-fold reductions, respectively. Moreover, secretion of TGF-β, 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-α-stimulated fibroblasts increased the NF-κB expression in colorectal cancer cell lines (HCT-116 and Sw48), while in the vicinity of ZER, the expression of NF-κB was reversed. Considering the significant effects of ZER, this component can be used as an appropriate alternative herbal treatment for cancer-related chronic inflammation.
炎症在几种癌症的发展中起着重要作用。炎性细胞因子，包括肿瘤坏死因子-α（TNF-α），与炎症的诱导有关。慢性炎症通过几种机制促进癌症的进展，包括增加细胞因子的产生和转录因子的激活，如核因子-κB（NF-κB）。姜黄（Zingiber zerumbet Smith）的一种成分莪术醇（ZER）似乎具有抗炎、抗癌和抗氧化作用。在这项研究中，我们旨在探讨 ZER 对 TNF-α诱导的促癌细胞因子的保护作用及其机制。我们发现，与未刺激的成纤维细胞（IC=40μmol/L）相比，用 ZER（IC=18μmol/L）处理刺激的人成纤维细胞系后，其活力降低。此外，ZER 抑制了 TNF-α诱导的成纤维细胞产生的转化生长因子-β（TGF-β）、白细胞介素-33（IL-33）、单核细胞趋化蛋白-1（MCP-1）和基质细胞衍生因子 1（SDF-1）的 mRNA 表达和蛋白分泌，这是通过定量实时 PCR（qRT-PCR）和 ELISA 测定的。TGF-β、IL-33、SDF-1 和 MCP-1 的 mRNA 表达水平分别降低了 8、5、2.5 和 4 倍。此外，与未处理组相比，TGF-β、IL-33、SDF-1 和 MCP-1 的分泌分别减少至 3.65±0.34ng/mL、6.3±0.26ng/mL、1703.6±295.2pg/mL 和 5.02±0.18pg/mL。此外，TNF-α刺激的成纤维细胞的条件培养基（CM）增加了结直肠癌细胞系（HCT-116 和 Sw48）中 NF-κB 的表达，而在 ZER 附近，NF-κB 的表达被逆转。考虑到 ZER 的显著作用，这种成分可以作为治疗与癌症相关的慢性炎症的一种合适的替代草药治疗方法。
