Androutsopoulos Vasilis P, Li Naichang, Arroo Randolph R J
Laboratory of Forensic Sciences and Toxicology, University of Crete, Heraklion, Voutes 71003, Greece.
J Nat Prod. 2009 Aug;72(8):1390-4. doi: 10.1021/np900051s.
Flavonoids have often been associated with cancer prevention and activity of the human cytochrome P450 enzymes CYP1A1 and CYP1B1 with the occurrence of cancer. The flavones eupatorin (1) and cirsiliol (2) enhanced CYP1 enzyme activity in a concentration-dependent manner in MCF7 human breast adenocarcinoma cells. In the range of 0-2.5 microM, 2 caused a dose-dependent increase in CYP1B1 mRNA levels and an increase in CYP1A1 mRNA. Compound 1 caused an increase in CYP1A1 and CYP1B1 mRNA at higher doses (approximately 5 microM). Both CYP1B1 and CYP1A1 catalyzed the conversion of 2 into an as yet unidentified compound. Application of the CYP1 family inhibitor, acacetin, significantly increased the IC(50) value of 2 in MCF7 cells, but did not significantly affect the action of 1. The data suggest that 2 induces CYP1 enzyme expression in cancer cells and is subsequently converted by CYP1B1 or CYP1A1 into an antiproliferative agent.
黄酮类化合物常与癌症预防以及人类细胞色素P450酶CYP1A1和CYP1B1的活性与癌症发生相关联。黄酮类化合物泽兰黄素（1）和刺槐素（2）在MCF7人乳腺腺癌细胞中以浓度依赖的方式增强了CYP1酶的活性。在0 - 2.5微摩尔范围内，2导致CYP1B1 mRNA水平呈剂量依赖性增加以及CYP1A1 mRNA增加。化合物1在较高剂量（约5微摩尔）时导致CYP1A1和CYP1B1 mRNA增加。CYP1B1和CYP1A1都催化2转化为一种尚未鉴定的化合物。应用CYP1家族抑制剂刺槐苷，显著增加了2在MCF7细胞中的IC(50)值，但对1的作用没有显著影响。数据表明2在癌细胞中诱导CYP1酶表达，随后被CYP1B1或CYP1A1转化为一种抗增殖剂。
