Suppression of interleukin 6 and 8 production in head and neck cancer cells with curcumin via inhibition of Ikappa beta kinase.
OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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-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.


CONCLUSIONS
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.
Cohen
Alen N
AN
Division of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095-1624, USA.
Veena
Mysore S
MS
Srivatsan
Eri S
ES
Wang
Marilene B
MB
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D003474:Curcumin