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Cancer Cell Biology
Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-B signaling
Sita Aggarwal 1, Yasunari Takada 1, Sujay Singh 2, Jeffrey N. Myers 3, Bharat B. Aggarwal 1 *
1Imgenex Corporation, San Diego, CA, USA
2Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
3Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
email: Bharat B. Aggarwal (aggarwal@mdanderson.org)
*Correspondence to Bharat B. Aggarwal, The University of Texas/M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 0143, Houston, TX 77030
Fax: +713-794-1613
Abstract
Increased expression of proinflammatory and proangiogenic factors are associated with aggressive tumor growth and decreased survival of patients with head and neck squamous cell carcinoma (HNSCC).
In as much as genes that are regulated by nuclear factor NF-B suppress apoptosis, induce proliferation, and mediate inflammation, angiogenesis and tumor metastasis, agents that suppress NF-B activation have potential as treatment for various cancers including HNSCC.
We demonstrate that all HNSCC cell lines expressed constitutively active NF-B and IB kinase (IKK), which is needed for NF-B activation.
Treatment of MDA 686LN cells with curcumin (diferuloylmethane), a pharmacologically safe chemopreventive agent, inhibited NF-B activation through abrogation of IKK. As a result expression of various cell survival and cell proliferative genes including Bcl-2, cyclin D1, IL-6, COX-2 and MMP-9 was suppressed.
This, in turn, inhibits proliferation of all HNSCC cell lines, arrests cell cycle in G1/S phase (MDA 686LN) and induces apoptosis as indicated by upstream and downstream caspase activation, PARP cleavage, annexin V staining in MDA 686LN cells.
Suppression of NF-B by cell-permeable p65-based peptide and NBD peptide also inhibited the proliferation and induced apoptosis in these cells.
Our results indicate that curcumin is a potent inhibitor of cell proliferation and an inducer of apoptosis in HNSCC through suppression of IKK-mediated NF-B activation and of NF-B-regulated gene expression.
International Journal of Cancer
Volume 111, Issue 5 , Pages 679 - 692
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