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Chemoprotective effects of capsaicin and diallyl sulfide against mutagenesis by vinyl carbamate and N-nitromethylamine

 Young-Joon Surh  ;  Richard Chieh-Jei Lee  ;  Kwang-Kyun Park  ;  Susan Taylor Mayne  ;  Amy Liem  ;  James A.Miller 
 CARCINOGENESIS, Vol.16(10) : 2467-2471, 1995-10 
Journal Title
Issue Date
Allyl Compounds* ; Animals ; Anticarcinogenic Agents / pharmacology ; Anticarcinogenic Agents / therapeutic use* ; Antimutagenic Agents / pharmacology* ; Capsaicin / analogs & derivatives ; Capsaicin / pharmacology ; Capsaicin / therapeutic use* ; Carcinogens / pharmacology ; Carcinogens / toxicity* ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System / metabolism ; Dimethylnitrosamine / toxicity* ; Disulfiram / pharmacology ; Dose-Response Relationship, Drug ; Female ; Mice ; Mice, Inbred ICR ; Mutagenicity Tests ; Mutagens / pharmacology* ; Salmonella typhimurium / drug effects ; Skin Neoplasms / chemically induced* ; Skin Neoplasms / prevention & control* ; Sulfides / pharmacology ; Sulfides / therapeutic use* ; Urethane / analogs & derivatives* ; Urethane / toxicity
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent and irritating ingredient of hot chilli peppers, which are frequently consumed as spices. This dietary phytochemical has been found to interact with microsomal xenobiotic metabolizing enzymes in rodents. Capsaicin and its saturated analog dihydrocapsaicin (trans-8-methyl-N-vanillyl-6-nonanamide) have been proposed to inactivate cytochrome P-450 HE1 by irreversibly binding to the active sites of the enzyme. Besides cytochrome P-450 HE1, other isoforms of the P-450 superfamily were also reported to be inhibited by capsaicin. The inhibition by capsaicin of microsomal monooxygenases involved in carcinogen activation implies its chemopreventive potential. As part of a program to investigate chemoprotective properties of capsaicin we initially determined the effect of capsaicin on vinyl carbamate (VC)- and N-nitrosodimethylamine (NDMA)-induced mutagenesis in Salmonella typhimurium TA100. Capsaicin (0.42 mM) attenuated the bacterial mutagenicity of VC and NDMA by 50% and 42% respectively. Diallyl sulfide, a thioether found in garlic with selective P-450 HE1 inhibitory activity, also lessened the mutagenicity of the above carcinogens in a concentration-dependent manner. The suppression of VC- and NDMA-induced mutagenesis by capsaicin and diallyl sulfide correlated with their inhibition of P-450 IIE1-mediated p-nitrophenol hydroxylation and NDMA N-demethylation. Pretreatment of female ICR mice with a topical dose of capsaicin lowered the average number of VC-induced skin tumors by 62% at 22 weeks after promotion. A similar degree of protection was attained with oral administration of diallyl sulfide before carcinogen treatment. The results of this study suggest that capsaicin and diallyl sulfide suppress VC- and NDMA-induced mutagenesis or tumorigenesis in part through inhibition of the cytochrome P-450 IIE1 isoform responsible for activation of these carcinogens.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Kwang Kyun(박광균)
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