Impact of eugenol and isoeugenol on AhR translocation, target gene expression, and proliferation in human HaCaT keratinocytes.
Identifieur interne : 000719 ( Main/Curation ); précédent : 000718; suivant : 000720Impact of eugenol and isoeugenol on AhR translocation, target gene expression, and proliferation in human HaCaT keratinocytes.
Auteurs : Michaela Kalmes [Allemagne] ; Brunhilde BlömekeSource :
- Journal of toxicology and environmental health. Part A [ 1528-7394 ] ; 2012.
English descriptors
- KwdEn :
- Antimetabolites, Blotting, Western, Bromodeoxyuridine, Cell Cycle Proteins (biosynthesis), Cell Cycle Proteins (genetics), Cell Line, Cell Proliferation (drug effects), Cell Survival (drug effects), Cytochrome P-450 CYP1A1 (metabolism), Eugenol (analogs & derivatives), Eugenol (pharmacology), G1 Phase (drug effects), Gene Expression (drug effects), Humans, Immunohistochemistry, Keratinocytes (drug effects), Protein Transport (drug effects), RNA, Messenger (biosynthesis), RNA, Messenger (genetics), Real-Time Polymerase Chain Reaction, Receptors, Aryl Hydrocarbon (drug effects), Receptors, Aryl Hydrocarbon (genetics), Resting Phase, Cell Cycle (drug effects), S Phase (drug effects), Signal Transduction (drug effects), Tetrazolium Salts.
- MESH :
- chemical , analogs & derivatives : Eugenol.
- chemical , biosynthesis : Cell Cycle Proteins, RNA, Messenger.
- chemical , drug effects : Receptors, Aryl Hydrocarbon.
- chemical , genetics : Cell Cycle Proteins, RNA, Messenger, Receptors, Aryl Hydrocarbon.
- chemical , metabolism : Cytochrome P-450 CYP1A1.
- chemical , pharmacology : Eugenol.
- chemical : Antimetabolites, Bromodeoxyuridine, Tetrazolium Salts.
- drug effects : Cell Proliferation, Cell Survival, G1 Phase, Gene Expression, Keratinocytes, Protein Transport, Resting Phase, Cell Cycle, S Phase, Signal Transduction.
- Blotting, Western, Cell Line, Humans, Immunohistochemistry, Real-Time Polymerase Chain Reaction.
Abstract
The phenolic derivatives eugenol and isoeugenol, which are naturally found in essential oils of different spices, are commonly used as fragrances. Recently data demonstrated that growth suppression produced by these substances occurs in keratinocytes and that the effects may be mediated via aryl hydrocarbon receptor (AhR) interactions. In this study the effects of eugenol and isoeugenol were determined on intracellular localization of AhR, AhR target gene expression, AhR-dependent cell cycle regulation, and proliferation in HaCaT cells. Both compounds produced a rapid and marked translocation of AhR into the nucleus, induced the expression of the AhR target genes cytochrome P-450 1A1 (CYP1A1) and AhR repressor (AhRR), and inhibited proliferation of HaCaT cells. Among the G(1) phase cell cycle-related proteins, levels of the retinoblastoma protein (RB), which is known to interact with AhR, and levels of the cyclin dependent kinase (CDK) 6 were reduced by eugenol and isoeugenol, whereas steady-state levels of CDK2 and CDK4 remained unaffected. Protein levels of CDK inhibitor (CKI) p27(KIP1), known to be modulated in an AhR-dependent manner, were increased after treatment with both substances. In conclusion, data show that the antiproliferative properties of eugenol and isoeugenol in HaCaT cells are mediated through AhR, and thereby the molecular mechanisms of action in these cells were identified for the first time in this study.
DOI: 10.1080/15287394.2012.674916
PubMed: 22686307
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pubmed:22686307Le document en format XML
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Part A</title><idno type="ISSN">1528-7394</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antimetabolites</term><term>Blotting, Western</term><term>Bromodeoxyuridine</term><term>Cell Cycle Proteins (biosynthesis)</term><term>Cell Cycle Proteins (genetics)</term><term>Cell Line</term><term>Cell Proliferation (drug effects)</term><term>Cell Survival (drug effects)</term><term>Cytochrome P-450 CYP1A1 (metabolism)</term><term>Eugenol (analogs & derivatives)</term><term>Eugenol (pharmacology)</term><term>G1 Phase (drug effects)</term><term>Gene Expression (drug effects)</term><term>Humans</term><term>Immunohistochemistry</term><term>Keratinocytes (drug effects)</term><term>Protein Transport (drug effects)</term><term>RNA, Messenger (biosynthesis)</term><term>RNA, Messenger (genetics)</term><term>Real-Time Polymerase Chain Reaction</term><term>Receptors, Aryl Hydrocarbon (drug effects)</term><term>Receptors, Aryl Hydrocarbon (genetics)</term><term>Resting Phase, Cell Cycle (drug effects)</term><term>S Phase (drug effects)</term><term>Signal Transduction (drug effects)</term><term>Tetrazolium Salts</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Eugenol</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cell Cycle Proteins</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Aryl Hydrocarbon</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cell Cycle Proteins</term><term>RNA, Messenger</term><term>Receptors, Aryl Hydrocarbon</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytochrome P-450 CYP1A1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Eugenol</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antimetabolites</term><term>Bromodeoxyuridine</term><term>Tetrazolium Salts</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Proliferation</term><term>Cell Survival</term><term>G1 Phase</term><term>Gene Expression</term><term>Keratinocytes</term><term>Protein Transport</term><term>Resting Phase, Cell Cycle</term><term>S Phase</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Blotting, Western</term><term>Cell Line</term><term>Humans</term><term>Immunohistochemistry</term><term>Real-Time Polymerase Chain Reaction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The phenolic derivatives eugenol and isoeugenol, which are naturally found in essential oils of different spices, are commonly used as fragrances. Recently data demonstrated that growth suppression produced by these substances occurs in keratinocytes and that the effects may be mediated via aryl hydrocarbon receptor (AhR) interactions. In this study the effects of eugenol and isoeugenol were determined on intracellular localization of AhR, AhR target gene expression, AhR-dependent cell cycle regulation, and proliferation in HaCaT cells. Both compounds produced a rapid and marked translocation of AhR into the nucleus, induced the expression of the AhR target genes cytochrome P-450 1A1 (CYP1A1) and AhR repressor (AhRR), and inhibited proliferation of HaCaT cells. Among the G(1) phase cell cycle-related proteins, levels of the retinoblastoma protein (RB), which is known to interact with AhR, and levels of the cyclin dependent kinase (CDK) 6 were reduced by eugenol and isoeugenol, whereas steady-state levels of CDK2 and CDK4 remained unaffected. Protein levels of CDK inhibitor (CKI) p27(KIP1), known to be modulated in an AhR-dependent manner, were increased after treatment with both substances. In conclusion, data show that the antiproliferative properties of eugenol and isoeugenol in HaCaT cells are mediated through AhR, and thereby the molecular mechanisms of action in these cells were identified for the first time in this study.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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