Suppression of Interleukin 6 and 8 Production in Head and Neck Cancer Cells With Curcumin via Inhibition of Iκβ Kinase

Abstract

To evaluate the effect of curcumin on production of interleukin 6 (IL-6) and 8 (IL-8) in head and neck squamous cell carcinoma (HNSCC) cell lines and to determine the mechanism by which these effects are modulated. Curcumin suppression of HNSCC is believed to be partly due to inhibition of the transcription factor nuclear factor-kappa beta (NF-kappa beta). Interleukin 6 and IL-8 are cytokines induced by NF-kappa beta activation with elevated levels in the serum of patients with HNSCC. We treated HNSCC cell lines CCL23, CAL27, UM-SCC1, and UM-SCC14A with increasing doses of curcumin and measured IL-6 and IL-8 levels using an enzyme-linked immunosorbent assay. Levels of NF-kappa beta, Ikappa beta kinase (IKK), and phosphorylated Ikappa beta were analyzed by means of Western blot. The IKK activity was measured in UM-SCC14A cells using an IKK-specific Ikappa beta alpha substrate after treatment with curcumin. Reverse transcription-polymerase chain reaction was performed to determine the effect of curcumin on the expression of IL-6 and IL-8. Curcumin treatment resulted in dose-dependent inhibition of IL-6 and IL-8 in all cell lines. All cell lines had similar NF-kappa beta levels; however, UM-SCC1 and UM-SCC14A had significantly higher Ikappa beta kinase levels and required considerably higher doses of curcumin before inhibition of IL-6 and IL-8 occurred. Curcumin treatment resulted in inhibition of IKK activity and inhibition of IL-6 and IL-8 expression. Curcumin significantly reduces IL-6 and IL-8 levels in HNSCC cell lines. This mechanism appears to be mediated via inhibition of Ikappa beta-kinase activity in the NF-kappa beta pathway. Interleukins 6 and 8 have potential use as biomarkers to measure the efficacy of treatment with curcumin.