Capsaicin suppresses phorbol ester-induced activation of NF-kappaB/Rel and AP-1 transcription factors in mouse epidermis.
Capsaicin, the principal pungent ingredient of hot chili peppers, has anti-inflammatory and analgesic properties and is currently used as a topical cream for the management of various neuropathic conditions. In the present study, topical application of capsaicin onto dorsal skin of female ICR mice strongly suppressed phorbol ester-stimulated activation of NF-kappaB via blockade of IkappaB-alpha degradation with subsequent inhibition of nuclear translocation of the functionally active NF-kappaB subunit, p65. Likewise, phorbol ester-induced activation of activator protein-1 (AP-1) was abolished by capsaicin pretreatment. Since altered transactivation of NF-kappaB and AP-1 has been implicated for neoplastic transformation and progression, the suppression of these transcription factors by capsaicin may account for its previously reported chemopreventive effects on mouse skin tumorigenesis as well as inflammation.
Han
S S
SS
College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, 151-742, Seoul, South Korea.
Keum
Y S
YS
Seo
H J
HJ
Chun
K S
KS
Lee
S S
SS
Surh
Y J
YJ
D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D051550:I-kappa B Kinase; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control; D010703:Phorbol Esters / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D012867:Skin / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051996:Transcription Factor RelA
D016328:NF-kappa B; D010703:Phorbol Esters; D020569:Proto-Oncogene Proteins c-rel; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D004247:DNA; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D013755:Tetradecanoylphorbol Acetate; D002211:Capsaicin