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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2010-9-2
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pubmed:abstractText |
Epidemiologic and animal studies revealed that capsaicin can act as a carcinogen or cocarcinogen. However, the molecular mechanisms of the cancer-promoting effects of capsaicin are not clear. Here, we report that capsaicin has a cocarcinogenic effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin carcinogenesis in vivo and is mediated through the epidermal growth factor receptor (EGFR), but not the transient receptor potential vanilloid subfamily member 1 (TRPV1). Topical application of capsaicin on the dorsal skin of 7,12-dimetylbenz(a)anthracene-initiated and TPA-promoted TRPV1 wild-type (WT) and TRPV1 knockout (KO) mice induced more and larger skin tumors in TRPV1/KO mice, suggesting a TRPV1-independent mechanism. Cyclooxygenase-2 (COX-2) was highly elevated by capsaicin treatment in tumors and murine embryonic fibroblasts from TRPV1/KO mice. Inhibitors of EGFR/MEK signaling suppressed TPA/capsaicin-induced COX-2 expression in TRPV1/KO cells, indicating that activation of EGFR and its downstream signaling is involved in COX-2 elevation. Capsaicin induced a further induction of TPA-increased COX-2 expression in EGFR/WT cells, but not in EGFR/KO cells. TPA/capsaicin cotreatment caused EGFR tyrosine phosphorylation and activated EGFR downstream signaling, including ERKs and Akt in EGFR/WT, but not EGFR/KO cells. Specific inhibition of EGFR and TRPV1 indicated that capsaicin-induced ERK activation in A431 cells was dependent on EGFR, but not TRPV1. Together, these findings suggest that capsaicin might act as a cocarcinogen in TPA-induced skin carcinogenesis through EGFR-dependent mechanisms.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/9,10-Dimethyl-1,2-benzanthracene,
http://linkedlifedata.com/resource/pubmed/chemical/Capsaicin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TRPV Cation Channels,
http://linkedlifedata.com/resource/pubmed/chemical/TRPV1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1538-7445
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6859-69
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pubmed:dateRevised |
2010-12-6
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pubmed:meshHeading |
pubmed-meshheading:20660715-9,10-Dimethyl-1,2-benzanthracene,
pubmed-meshheading:20660715-Animals,
pubmed-meshheading:20660715-Capsaicin,
pubmed-meshheading:20660715-Carcinoma, Squamous Cell,
pubmed-meshheading:20660715-Cell Line, Tumor,
pubmed-meshheading:20660715-Cocarcinogenesis,
pubmed-meshheading:20660715-Cyclooxygenase 2,
pubmed-meshheading:20660715-Drug Synergism,
pubmed-meshheading:20660715-Enzyme Activation,
pubmed-meshheading:20660715-Female,
pubmed-meshheading:20660715-Humans,
pubmed-meshheading:20660715-Male,
pubmed-meshheading:20660715-Mice,
pubmed-meshheading:20660715-Mice, Knockout,
pubmed-meshheading:20660715-Receptor, Epidermal Growth Factor,
pubmed-meshheading:20660715-Signal Transduction,
pubmed-meshheading:20660715-Skin Neoplasms,
pubmed-meshheading:20660715-TRPV Cation Channels,
pubmed-meshheading:20660715-Tetradecanoylphorbol Acetate,
pubmed-meshheading:20660715-src-Family Kinases
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pubmed:year |
2010
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pubmed:articleTitle |
Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1.
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pubmed:affiliation |
Department of Bioscience and Biotechnology, Konkuk University, Seoul, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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