Abstract
Epidermal Growth Factor Receptor (EGFR) mutants are associated with resistance to chemotherapy, radiation, and targeted therapies. Here we found that the phytochemical 3,3'-Diindolylmethane (DIM) can inhibit the growth and also the invasion of breast cancer, glioma, and non-small cell lung cancer cells regardless of which EGFR mutant is expressed and the drug-resistant phenotype. DIM reduced an array of growth factor signaling pathways and altered cell cycle regulators and apoptotic proteins favoring cell cycle arrest and apoptosis. Therefore, DIM may be used in treatment regimens to inhibit cancer cell growth and invasion, and potentially overcome EGFR mutant-associated drug resistance.
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Cycle / drug effects
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Cell Survival / drug effects
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Drug Resistance, Neoplasm*
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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Female
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Genes, erbB-1
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Glioma / drug therapy*
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Glioma / genetics
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Glioma / metabolism
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Glioma / pathology
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Humans
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Indoles / pharmacology*
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Indoles / therapeutic use
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Mutant Proteins / metabolism
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Mutation
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Neoplasm Invasiveness
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Phosphorylation
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Receptor Protein-Tyrosine Kinases / metabolism
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Signal Transduction / drug effects
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Stress, Physiological
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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Indoles
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Mutant Proteins
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EGFR protein, human
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ErbB Receptors
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Receptor Protein-Tyrosine Kinases
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3,3'-diindolylmethane