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Curcumin treatment suppresses IKK? kinase activity of salivary cells of patients with head and neck cancer: a pilot study.

ABSTRACT: PURPOSE:To determine whether curcumin would inhibit I?B kinase ? (IKK?) kinase activity and suppress expression of proinflammatory cytokines in head and neck squamous cell carcinoma cancer (HNSCC) patients. EXPERIMENTAL DESIGN:Saliva was collected before and after subjects chewed curcumin tablets. Protein was extracted and IKK? kinase activity measured. Interleukin (IL)-6 and IL-8 levels in the salivary supernatants were measured by ELISA. IL-6, IL-8, and other interleukin were also measured independently with ELISA to confirm the inhibitory effect of curcumin on expression and secretion of salivary cytokines. RESULTS:Curcumin treatment led to a reduction in IKK? kinase activity in the salivary cells of HNSCC patients (P < 0.05). Treatment of UM-SCC1 cells with curcumin as well as with post-curcumin salivary supernatant showed a reduction of IKK? kinase activity. Significant reduction of IL-8 levels (P < 0.05) was seen in post-curcumin samples from patients with dental caries. Although there was reduced IL-8 expression in 8 of 21 post-curcumin samples of HNSCC patients, the data did not reach statistical significance. Saliva samples from HNSCC patients were also analyzed in a blinded fashion for expression of cytokines. IL-10, IFN-?, IL-12p70, and IL-2 clustered together, and granulocyte macrophage colony stimulating factor and TNF-? clustered together. Log?? ratio analysis showed decrease in expression of all nine cytokines in both the salivary supernatant and salivary cells of curcumin-treated samples. CONCLUSIONS:Curcumin inhibited IKK? kinase activity in the saliva of HNSCC patients, and this inhibition correlated with reduced expression of a number of cytokines. IKK? kinase could be a useful biomarker for detecting the effect of curcumin in head and neck cancer.

SUBMITTER: Kim SG

PROVIDER: S-EPMC3176971 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Curcumin treatment suppresses IKKβ kinase activity of salivary cells of patients with head and neck cancer: a pilot study.

Kim Suejung G SG Veena Mysore S MS Basak Saroj K SK Han Eugene E Tajima Tracey T Gjertson David W DW Starr Joshua J Eidelman Ofer O Pollard Harvey B HB Srivastava Meera M Srivatsan Eri S ES Wang Marilene B MB

Clinical cancer research : an official journal of the American Association for Cancer Research 20110805 18

<h4>Purpose</h4>To determine whether curcumin would inhibit IκB kinase β (IKKβ) kinase activity and suppress expression of proinflammatory cytokines in head and neck squamous cell carcinoma cancer (HNSCC) patients.<h4>Experimental design</h4>Saliva was collected before and after subjects chewed curcumin tablets. Protein was extracted and IKKβ kinase activity measured. Interleukin (IL)-6 and IL-8 levels in the salivary supernatants were measured by ELISA. IL-6, IL-8, and other interleukin were al ...[more]

PMID: 21821700

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Project description:The inhibitor-?B kinase-nuclear factor-?B (IKK-NF-?B) and epidermal growth factor receptor-activator protein-1 (EGFR-AP1) pathways are often co-activated and promote malignant behavior, but the underlying basis for this relationship is unclear. Resistance to inhibitors of IKK? or EGFR is observed in head and neck squamous cell carcinomas (HNSCC). Here, we reveal that both IKK? and ? contribute to nuclear activation of canonical and alternate NF-?B/REL family transcription factors, and overexpression of signal components that enhance co-activation of the EGFR-AP1 pathway. We observed that IKK? and IKK? exhibit increased protein expression, nuclear localization, and phosphorylation in HNSCC tissues and cell lines. Individually, IKK activity varied among different cell lines, but overexpression of both IKKs induced the strongest NF-?B activation. Conversely, siRNA knock down of both IKKs significantly decreased nuclear localization and phosphorylation of canonical RELA and I?B? and alternative p52 and RELB subunits. Knock down of both IKKs more effectively inhibited NF-?B activation, broadly modulated gene expression and suppressed cell proliferation and migration. Global expression profiling revealed that NF-?B, cytokine, inflammatory response and growth factor signaling are among the top pathways and networks regulated by IKKs. Importantly, IKK? and IKK? together promoted the expression and activity of transforming growth factor ?, EGFR and AP1 transcription factors cJun, JunB and Fra1. Knock down of AP1 subunits individually decreased 8/15 (53%) of IKK-targeted genes sampled and similarly inhibited cell proliferation and migration. Mutations of NF-?B and AP1-binding sites abolished or decreased IKK-induced interleukin-8 (IL-8) promoter activity. Compounds such as wedelactone with dual IKK inhibitory activity and geldanomycins that block IKK?/? and EGFR pathways were more active than IKK?-specific inhibitors in suppressing NF-?B activation and proliferation and inducing cell death. We conclude that IKK? and IKK? cooperatively activate NF-?B and EGFR/AP1 networks of signaling pathways and contribute to the malignant phenotype and the intrinsic or acquired therapeutic resistance of HNSCC.

Dataset Information

Curcumin treatment suppresses IKK? kinase activity of salivary cells of patients with head and neck cancer: a pilot study.

Publications

Curcumin treatment suppresses IKKβ kinase activity of salivary cells of patients with head and neck cancer: a pilot study.

Similar Datasets

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