Surh Y J, Lee R C, Park K K, Mayne S T, Liem A, Miller J A
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
Carcinogenesis. 1995 Oct;16(10):2467-71. doi: 10.1093/carcin/16.10.2467.
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.
辣椒素（反式-8-甲基-N-香草基-6-壬酰胺）是干辣椒中的一种主要辛辣刺激性成分，干辣椒常被用作香料。这种膳食植物化学物质已被发现可与啮齿动物体内的微粒体异生物质代谢酶相互作用。有人提出辣椒素及其饱和类似物二氢辣椒素（反式-8-甲基-N-香草基-6-壬酰胺）通过不可逆地结合到细胞色素P-450 HE1的活性位点而使其失活。除了细胞色素P-450 HE1外，还报道了P-450超家族的其他同工酶也受到辣椒素的抑制。辣椒素对参与致癌物激活的微粒体单加氧酶的抑制作用暗示了其化学预防潜力。作为研究辣椒素化学保护特性计划的一部分，我们最初测定了辣椒素对鼠伤寒沙门氏菌TA100中氨基甲酸乙烯酯（VC）和N-亚硝基二甲胺（NDMA）诱导的诱变作用的影响。辣椒素（0.42 mM）分别使VC和NDMA的细菌诱变性降低了50%和42%。二烯丙基硫醚是大蒜中发现的一种具有选择性P-450 HE1抑制活性的硫醚，它也以浓度依赖的方式降低了上述致癌物的诱变性。辣椒素和二烯丙基硫醚对VC和NDMA诱导的诱变作用的抑制与它们对P-450 IIE1介导的对硝基苯酚羟基化和NDMA N-去甲基化的抑制相关。用局部剂量的辣椒素预处理雌性ICR小鼠，在促癌22周后，可使VC诱导的皮肤肿瘤平均数量降低62%。在致癌物处理前口服二烯丙基硫醚也能获得类似程度的保护。这项研究的结果表明，辣椒素和二烯丙基硫醚部分通过抑制负责激活这些致癌物的细胞色素P-450 IIE1同工型来抑制VC和NDMA诱导的诱变或肿瘤发生。
