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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion
Joell J Gills1, Elizabeth H Jeffery, Nathan V Matusheski
1Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Abstract:
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.
Insights
Sulforaphane (SF), a natural compound from broccoli, effectively inhibited skin tumor development in mice when applied after carcinogen exposure. SF also reduced a key enzyme activity linked to tumor promotion.
Area of Science:
- Chemoprevention
- Natural Products
- Cancer Research
Background:
- Sulforaphane (SF) is a natural compound found in broccoli with known anti-carcinogenic properties.
- Previous studies suggest SF inhibits tumor growth, cell cycle progression, and induces apoptosis.
- SF's role in blocking chemical carcinogenesis initiation and promotion has been investigated.
Purpose of the Study:
- To evaluate the efficacy of topical Sulforaphane (SF) in preventing mouse skin tumorigenesis.
- To investigate the effect of SF on specific molecular mechanisms involved in carcinogenesis, such as ornithine decarboxylase activity.
Main Methods:
- Topical application of SF (1, 5, or 10 micromol/mouse) in mouse skin tumorigenesis models induced by 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol 13-acetate (TPA).
- SF was administered using anti-promotion and combined anti-initiation/anti-promotion protocols.
- Measurement of TPA-induced ornithine decarboxylase activity in mouse skin.
Main Results:
- Topical SF significantly inhibited TPA-induced mouse skin tumorigenesis under anti-promotion and combined protocols.
- SF did not show a significant effect when applied solely as an anti-initiation treatment.
- SF administration inhibited TPA-induced ornithine decarboxylase activity in mouse skin.
Conclusions:
- Sulforaphane demonstrates significant chemopreventive effects against mouse skin tumorigenesis, particularly when applied during the promotion phase.
- The inhibition of ornithine decarboxylase activity by SF is a key molecular mechanism underlying its anti-promotion effects.
- SF's efficacy is dependent on the timing of application relative to carcinogen exposure.
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