Abstract
We studied the chemopreventive efficacy of indole-3-carbinol (I3C), a phytochemical found in cruciferous vegetables, to inhibit tobacco carcinogen-induced lung adenocarcinoma in A/J mice when given following post-initiation or progression protocol. Moreover, we assessed the potential mechanisms responsible for the anticancer effects of I3C. Post-initiation administration of I3C decreased the multiplicity of surface tumors as well as all forms of histopathological lesions, including adenocarcinoma, whereas administration of the compound during tumor progression failed to decrease the multiplicity of surface tumors and early forms of microscopic lesions but reduced the frequency of adenocarcinoma. Mechanistic studies in A549 lung adenocarcinoma cells indicated that the lung cancer preventive effects of I3C are mediated, at least in part, via modulation of the receptor tyrosine kinase/PI3K/Akt signaling pathway.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenocarcinoma / chemically induced
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma / prevention & control*
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Adenocarcinoma of Lung
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Animals
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Anticarcinogenic Agents / pharmacology*
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Carcinogens / toxicity
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Cell Growth Processes / drug effects
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Cell Transformation, Neoplastic / chemically induced
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Cell Transformation, Neoplastic / drug effects*
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Female
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Humans
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Indoles / pharmacology*
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Lung Neoplasms / chemically induced
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Lung Neoplasms / prevention & control*
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Mice
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Mice, Inbred A
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Nitrosamines / antagonists & inhibitors*
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Nitrosamines / toxicity
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Oncogene Protein v-akt / antagonists & inhibitors
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Oncogene Protein v-akt / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptor Protein-Tyrosine Kinases / metabolism
Substances
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Anticarcinogenic Agents
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Carcinogens
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Indoles
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Nitrosamines
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Phosphoinositide-3 Kinase Inhibitors
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4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
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indole-3-carbinol
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Receptor Protein-Tyrosine Kinases
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Oncogene Protein v-akt