Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion.
Sulforaphane (SF), a natural product from broccoli, is known to enhance detoxification of carcinogens and block initiation of chemically-induced carcinogenesis in animal models. Cell culture and xenograft studies suggest additional roles for SF, inhibiting growth of tumors, arresting the cell cycle and enhancing apoptosis. As currently reported, topical SF (1, 5 or 10 micromol/mouse) significantly inhibited 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse skin tumorigenesis, using either an anti-promotion protocol (SF from 1 week after carcinogen until the end of the study) or a combined anti-initiation, anti-promotion protocol (SF 7 days prior to carcinogen until the end of the study). Surprisingly, no significant effect was observed in an anti-initiation protocol (SF from 7 days prior to 7 days after carcinogen). Separately, SF inhibited TPA-induced ornithine decarboxylase activity in mouse skin, an obligate step in TPA-induced promotion of carcinogenesis. These data link this molecular mechanism to SF-dependent inhibition of the promotion of tumorigenesis.
Gills
Joell J
JJ
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Jeffery
Elizabeth H
EH
Matusheski
Nathan V
NV
Moon
Richard C
RC
Lantvit
Daniel D
DD
Pezzuto
John M
JM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001937:Brassica; D002273:Carcinogens; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D017879:Isothiocyanates; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013454:Sulfoxides; D013755:Tetradecanoylphorbol Acetate; D013861:Thiocyanates / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D017879:Isothiocyanates; D065108:Ornithine Decarboxylase Inhibitors; D013454:Sulfoxides; D013861:Thiocyanates; D015127:9,10-Dimethyl-1,2-benzanthracene; D009955:Ornithine Decarboxylase; C016766:sulforaphane; D013755:Tetradecanoylphorbol Acetate