Abstract
NF-kappaB is activated in many types of cancer. Phosphorylation of p65 at serine 276 is required for the expression of a subset of NF-kappaB regulated genes, including vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8). Thus, inhibition of serine 276 phosphorylation may prevent metastasis and angiogenesis in certain tumor types. Using in silico molecular docking, small molecules that are predicted to bind to a structural pocket near serine 276 were identified. One compound, NSC-127102, hinders serine 276 phosphorylation and the expression of IL-8 and VCAM-1. Small molecules such as NSC-127102 may be optimized for the future treatment of cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antineoplastic Agents / pharmacology
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Breast Neoplasms / genetics
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Carcinoma, Hepatocellular / genetics
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Cell Line, Tumor
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Cyclic AMP Response Element-Binding Protein / drug effects
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Cyclic AMP Response Element-Binding Protein / metabolism
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DNA, Complementary / genetics
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Female
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Humans
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Interleukin-8 / genetics
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Liver Neoplasms / genetics
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NF-kappa B / metabolism*
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Phosphoserine / antagonists & inhibitors
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Phosphoserine / metabolism
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Protein Subunits / antagonists & inhibitors
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Protein Subunits / metabolism
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RNA, Neoplasm / genetics
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RNA, Neoplasm / isolation & purification
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
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Vascular Cell Adhesion Molecule-1 / genetics
Substances
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Antineoplastic Agents
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Cyclic AMP Response Element-Binding Protein
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DNA, Complementary
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Interleukin-8
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NF-kappa B
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Protein Subunits
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RNA, Neoplasm
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Vascular Cell Adhesion Molecule-1
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Phosphoserine