Department of Food Science and Nutrition, University of Minnesota, 225 Food Science and Nutrition, 1334 Eckles Avenue, St. Paul, MN, 55108-1038, USA.
Protein J. 2011 Oct;30(7):447-56. doi: 10.1007/s10930-011-9350-0.
Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens may be an important chemopreventive mechanism. Consumption of apiaceous vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many furanocoumarins are potent inhibitors of several CYPs, we characterized the effects of three furanocoumarins from apiaceous vegetables on human CYP1A2 (hCYP1A2). We assessed hCYP1A2 methoxyresorufin O-demethylase (MROD) activity using microsomes from Saccharomyces cerevisiae expressing hCYP1A2. Isopimpinellin exhibited mechanism-based inactivation (MBI) of hCYP1A2 (K(i) = 1.2 μM, k (inact) = 0.34 min⁻¹, and partition ratio = 8). Imperatorin and trioxsalen were characterized as mixed inhibitors with K(i) values of 0.007 and 0.10 μM, respectively. These results indicate that even if present at low levels in apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute significantly to CYP1A2 inhibition and potentially decreased procarcinogen activation. Moreover, the in vivo effect of isopimpinellin on CYP1A2 may be longer lasting compared to reversible inhibitors.
细胞色素 P-450 1A2（CYP1A2）介导的前致癌物激活的抑制可能是一种重要的化学预防机制。食用伞形科蔬菜（富含呋喃香豆素）可抑制人体内的 CYP1A2。由于许多呋喃香豆素是几种 CYP 的有效抑制剂，因此我们研究了三种来自伞形科蔬菜的呋喃香豆素对人 CYP1A2（hCYP1A2）的影响。我们使用表达 hCYP1A2 的酿酒酵母微粒体评估了 hCYP1A2 甲氧基resorufin O-脱甲基酶（MROD）活性。异茴芹素表现出 hCYP1A2 的基于机制的失活（MBI）（K(i) = 1.2 μM，k (inact) = 0.34 min⁻¹，和分配比 = 8）。欧前胡素和补骨脂素被表征为混合抑制剂，其 K(i) 值分别为 0.007 和 0.10 μM。这些结果表明，即使在伞形科蔬菜中含量较低，欧前胡素、补骨脂素和异茴芹素也可能对 CYP1A2 抑制和潜在的前致癌物激活产生重大影响。此外，与可逆抑制剂相比，异茴芹素对 CYP1A2 的体内作用可能持续时间更长。
