Suppression of the TPA-induced expression of nuclear-protooncogenes in mouse epidermis by crocetin via antioxidant activity.
Crocetin, a major component of the fruit of Gardenia jasminoides Ellis, was investigated for its antitumor promoting effect on 12-O-tetradecanoylphorbol-13-acetate-promoted mouse skin carcinogenesis. Topical application of 5 nmol TPA to CD-1 mice once daily for 5 days caused epidermal hyperplasia, and increases in the levels of c-Fos, c-Jun and c-Myc in the suprabasal layer of epidermis and the muscle layer of dermis. Immunocytolochemical examination showed that pretreatment of 1 mumol crocetin repressed the TPA-induced epidermal hyperplasia and the expressions of c-Jun, c-Fos and c-Myc to the extent of 47, 44 and 45% respectively. Crocetin of 3.0 mumol exhibited stronger inhibition on the induced hyperplasia and the oncoproteins levels (by 60, 53 and 55% respectively). Western blotting analysis confirmed this inhibitory effect of crocetin. Pretreatment of crocetin also repressed the TPA-induced H2O2 production and myeloperoxidase activity. These data indicate that crocetin suppresses the TPA-induced skin carcinogenesis maybe via its antioxidant property which, in turn, leads to a reduction in the TPA-induced expressions of c-Jun, c-Fos and c-Myc in mouse epidermis.
Hsu
J D
JD
Department of Pathology, Chung Shan Medical and Dental College Hospital, Taichung, Taiwan.
Chou
F P
FP
Lee
M J
MJ
Chiang
H C
HC
Lin
Y L
YL
Shiow
S J
SJ
Wang
C J
CJ
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002338:Carotenoids / Q000008:administration & dosage / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism*; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives
D000975:Antioxidants; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D006861:Hydrogen Peroxide; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate