Teel R W, Huynh H
Department of Physiology and Pharmacology, Loma Linda University, CA 92350, USA.
Cancer Lett. 1998 Nov 27;133(2):135-41. doi: 10.1016/s0304-3835(98)00218-3.
Compounds derived from plant sources with putative anticancer properties were studied for their effects on alkoxyresorufin O-dealkylase activity, a measure of cytochrome P450 activity. The phytochemicals investigated included benzyl isothiocyanate, caffeic acid, chlorogenic acid, diosmin, ferulic acid, indole-3-carbinol, phenethyl isothiocyanate and resveratrol. Each phytochemical at concentrations of 0.25 and 0.5 microM was incubated with 0.2 mg hamster liver microsomal protein and 0.5 microM concentrations of benzyloxyresorufin, ethoxyresorufin and methoxyresorufin. Three of the phytochemicals tested, namely benzyl isothiocyanate, phenethyl isothiocyanate and resveratrol, exhibited potent inhibition of alkoxyresorufin O-dealkylase activity. Benzyl isothiocyanate inhibited benzyloxyresorufin O-dealkylase (BROD) activity, ethoxyresorufin O-deethylase (EROD) activity and methoxyresorufin O-demethylase (MROD) activity by 90% at both the 0.25 and 0.5 microM concentrations. Phenethyl isothiocyanate inhibited BROD activity by 69%, EROD activity by 90% and MROD activity by 94% at both concentrations tested. Resveratrol inhibited BROD activity by 69% at the 0.25 microM concentration and by 78% at the 0.5 microM concentration. It inhibited EROD activity by 60% at the 0.25 microM concentration and by 80% at the 0.5 microM concentration. Resveratrol exhibited the greatest inhibitory action toward MROD, i.e. 76% and 84% at the two concentrations tested. Chlorogenic acid significantly affected BROD, EROD and MROD activity only at the 0.5 microM concentration inhibiting by 51%, 47% and 54%, respectively. Caffeic acid affected BROD and MROD activity at 0.5 microM only inhibiting BROD activity by 46% and MROD activity by 40%. Diosmin inhibited EROD activity by 11% at the 0.25 microM concentration and by 61% at 0.5 microM. It inhibited MROD by 47% and 54% at the two concentrations tested but did not significantly alter BROD activity. Ferulic acid significantly inhibited EROD and MROD activity at the 0.5 microM concentration by 28% and 32%, respectively. Indole-3-carbinol significantly inhibited BROD activity by 26% at 0.25 microM and by 42% at 0.5 microM. It inhibited EROD and MROD activity by 28% and 29% at 0.5 microM, respectively. The alkoxyresorufin O-dealkylase reactions are selective for various isoforms of cytochrome P450. Our results suggest that the phytochemicals we tested have varied effects on the enzymatic activity of isoforms of cytochrome P450 that dealkylate benzyloxyresorufin, methoxyresorufin and ethoxyresorufin and therefore may have varied effects on the metabolism of substrates for these isoforms.
对源自植物、具有假定抗癌特性的化合物进行了研究，考察它们对烷氧基试卤灵O - 脱烷基酶活性的影响，以此作为细胞色素P450活性的一种度量。所研究的植物化学物质包括苄基异硫氰酸酯、咖啡酸、绿原酸、地奥司明、阿魏酸、吲哚 - 3 - 甲醇、苯乙基异硫氰酸酯和白藜芦醇。每种植物化学物质在浓度为0.25微摩尔和0.5微摩尔时，分别与0.2毫克仓鼠肝脏微粒体蛋白以及0.5微摩尔浓度的苄氧基试卤灵、乙氧基试卤灵和甲氧基试卤灵一起孵育。所测试的三种植物化学物质，即苄基异硫氰酸酯、苯乙基异硫氰酸酯和白藜芦醇，对烷氧基试卤灵O - 脱烷基酶活性表现出强效抑制作用。苄基异硫氰酸酯在0.25微摩尔和0.5微摩尔浓度时，对苄氧基试卤灵O - 脱烷基酶（BROD）活性、乙氧基试卤灵O - 脱乙基酶（EROD）活性和甲氧基试卤灵O - 脱甲基酶（MROD）活性的抑制率均达90%。苯乙基异硫氰酸酯在两个测试浓度下，对BROD活性的抑制率为69%，对EROD活性的抑制率为90%，对MROD活性的抑制率为94%。白藜芦醇在0.25微摩尔浓度时对BROD活性的抑制率为应为69%，在0.5微摩尔浓度时为78%。它在0.25微摩尔浓度时对EROD活性的抑制率为60%，在0.5微摩尔浓度时为80%。白藜芦醇对MROD表现出最大抑制作用，即在两个测试浓度下分别为76%和84%。绿原酸仅在0.5微摩尔浓度时对BROD、EROD和MROD活性有显著影响，抑制率分别为51%、47%和54%。咖啡酸仅在0.5微摩尔时对BROD和MROD活性有影响，对BROD活性的抑制率为46%，对MROD活性的抑制率为40%。地奥司明在0.25微摩尔浓度时对EROD活性的抑制率为11%，在0.5微摩尔浓度时为61%。在两个测试浓度下，它对MROD的抑制率分别为47%和54%，但对BROD活性无显著改变。阿魏酸在0.5微摩尔浓度时对EROD和MROD活性有显著抑制作用，抑制率分别为28%和32%。吲哚 - 3 - 甲醇在0.25微摩尔时对BROD活性的抑制率为26%，在0.5微摩尔时为42%。在0.5微摩尔时，它对EROD和MROD活性的抑制率分别为28%和29%。烷氧基试卤灵O - 脱烷基酶反应对细胞色素P450的各种同工型具有选择性。我们的结果表明，我们所测试的植物化学物质对使苄氧基试卤灵、甲氧基试卤灵和乙氧基试卤灵脱烷基的细胞色素P450同工型的酶活性有不同影响，因此可能对这些同工型底物的代谢有不同影响。
