Hesperetin, a Citrus bioflavonoid, prevents IL-1β-induced inflammation and cell proliferation in lung epithelial A549 cells

ABSTRACT

Hesperetin, a Citrus bioflavonoid, exhibits anticancer, anti-inflammatory and antioxidant properties. However, its action and mechanism in inflammation-induced lung cancer is unknown. We have investigated anticancer effects of hesperetin in IL-1β-stimulated lung adenocarcinoma cell proliferation and COX-2 -mediated inflammation. The human lung adenocarcinoma A549 cells were serum-starved with or without HN (100 μM) for overnight and stimulated with IL-1β for varying durations. Cell viability and proliferation were assessed by MTT and wound healing assays. Cell cycle progression was measured by flow cytometry, and RT-PCR and immunoblotting methods were used to examine the expression COX-2 mRNA and protein, respectively. Protein stability assessed by cycloheximide chase assay. IL-1β caused a time- and dose-dependent increase in cell viability and proliferation, expression of COX-2 at transcription as well as translation levels, increased the stability of COX-2 protein, and PGE2 production while HN significantly decreased these changes. Further, IL-1β stimulated increased phosphorylation of ERK-1/2 and p65 subunit of NF-κB, which were reversed by HN in A549 cells. These results show that HN could inhibit IL-1β-stimulated cell proliferation, COX-2 expression and its regulation at translation level and PGE2 synthesis in A549 lung epithelial cells, indicating its anti-inflammatory and anticancer potential in lung cancer cells.