Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan.
Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan.
Chem Biol Interact. 2018 Aug 25;292:101-109. doi: 10.1016/j.cbi.2018.07.010. Epub 2018 Jul 19.
Nickel exposure promotes the invasive potential of human lung cancer cells. Polyphenols such as quercetin, curcumin, chrysin, apigenin, and luteolin, present in many plant foods may suppress the development of cancers. However, whether these compounds inhibit the promoting effects of Nickel on cancer cell invasion and migration as well as the possible mechanisms are unclear. In the present study, we first showed that quercetin, curcumin, chrysin, apigenin, and luteolin at 5 μM, significantly suppressed the promoting effects of NiCl (Ni) on migration and invasion in H1975 and A549 human lung cancer cells. The five phytochemicals also significantly suppressed the secretion of cytokines, IL-1β, IL-6, TNF-α and IL-10, induced by Ni in A549 cells. The overall efficiency of quercetin was the best, followed by chrysin and the other compounds. Furthermore, we found that quercetin and chrysin suppressed the mRNA and protein expression of TLR4 and Myd88. Consistently, quercetin and chrysin also decreased the phosphorylation of IKKβ and IκB, the nuclear level of p65 (NF-κB) as well as the expression of MMP-9 in A549 cells exposed to Ni. In conclusion, these results suggest the potential preventive effects of the five phytochemicals on the promoting effect of Ni on human lung cancer cell invasion. In addition, the preventive effects are associated with downregulation of the TLR4/NF-κB signaling pathway, especially for quercetin and chrysin.
镍暴露促进了人类肺癌细胞的侵袭能力。存在于许多植物性食物中的多酚类物质，如槲皮素、姜黄素、白杨素、芹菜素和木樨草素，可能抑制癌症的发展。然而，这些化合物是否抑制镍对癌细胞侵袭和迁移的促进作用，以及可能的机制尚不清楚。在本研究中，我们首先表明，槲皮素、姜黄素、白杨素、芹菜素和木樨草素在 5µM 时，显著抑制了 NiCl（Ni）对 H1975 和 A549 人肺癌细胞迁移和侵袭的促进作用。这五种植物化学物质也显著抑制了 Ni 在 A549 细胞中诱导的细胞因子 IL-1β、IL-6、TNF-α 和 IL-10 的分泌。槲皮素的整体效果最好，其次是白杨素和其他化合物。此外，我们发现槲皮素和白杨素抑制了 TLR4 和 Myd88 的 mRNA 和蛋白表达。一致地，槲皮素和白杨素也降低了 A549 细胞中 Ni 诱导的 IKKβ 和 IκB 的磷酸化、p65（NF-κB）的核水平以及 MMP-9 的表达。总之，这些结果表明这五种植物化学物质对 Ni 促进人肺癌细胞侵袭的潜在预防作用。此外，预防作用与 TLR4/NF-κB 信号通路的下调有关，尤其是槲皮素和白杨素。
