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

Alen N. Cohen, MD; Mysore S. Veena, PhD; Eri S. Srivatsan, PhD; Marilene B. Wang, MD

Arch Otolaryngol Head Neck Surg. 2009;135(2):190-197.

Objectives  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-β (NF-β). Interleukin 6 and IL-8 are cytokines induced by NF-β activation with elevated levels in the serum of patients with HNSCC.

Design  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.

Setting  Levels of NF-β, Iβ kinase (IKK), and phosphorylated Iβ were analyzed by means of Western blot. The IKK activity was measured in UM-SCC14A cells using an IKK-specific Iβ substrate after treatment with curcumin.

Main Outcome Measures  Reverse transcription–polymerase chain reaction was performed to determine the effect of curcumin on the expression of IL-6 and IL-8.

Results  Curcumin treatment resulted in dose-dependent inhibition of IL-6 and IL-8 in all cell lines. All cell lines had similar NF-β levels; however, UM-SCC1 and UM-SCC14A had significantly higher Iβ 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.

Conclusions  Curcumin significantly reduces IL-6 and IL-8 levels in HNSCC cell lines. This mechanism appears to be mediated via inhibition of Iβ-kinase activity in the NF-β pathway. Interleukins 6 and 8 have potential use as biomarkers to measure the efficacy of treatment with curcumin.

Author Affiliations: Division of Head and Neck Surgery (Drs Cohen and Wang), Department of Surgery (Drs Veena and Srivatsan), David Geffen School of Medicine, University of California, Los Angeles, and Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System (Drs Veena, Srivatsan, and Wang).

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