Quercetin and chrysin inhibit nickel-induced invasion and migration by downregulation of TLR4/NF-κB signaling in A549 cells

Abstract

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 NiCl₂ (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.

Keywords: Chrysin; Lung cancer cell; NF-κB; Nickel; Quercetin; TLR4.