Metabolism of Formosanin-C by Cytochrome P-450

Cytochrome P-450對Formosanin C之代謝作用

黃正一(Cheng-Yi Huang) ； 周光儀(Kang-Yi Chou) ； 江雪卿(Hsuch-Ching Chiang)

《Journal of Medical Sciences》 10卷1期 (1989/02) Pp. 25-32

摘要

七葉蓮的主要成份PF-3為類脂醇配糖體具實驗性抗肝癌活性，亦具卵巢腫瘤及大腸癌抑制效果。從PF-3離體實驗發現肝臟微粒體胞色素P-450酵素的oxygen binding site可結合FP-3產生Type II的Difference spectrum，Ks值是78μM，Amax 值是0.21。由一氧化碳的抑制NADPH-generating system可因phenobarbital的作用而加強。此一事實證明以phenobarbital所誘導的cytochrome P-450的isoenzyme 參予且活化PF-3的代謝作用。

關鍵字

七葉蓮 ； 胞色素P-450

並列摘要

Fonnosanin c is a steroidal glycoside isolated from Paris fonnosana Hayata. It has been known from the previous studies, the growth of solid MH134 mice hepatoma was retarded by 1-2.5 mg/kg Fonnosanin c, and also significant regression in tumor SK-OV-3 (ovary) and HT-29 (colon) was induced by PF-3. The biotransfonnation of fonnosanin c by hepatic cytochrome P-450 has been investigated. The hepatic microsomal cytochrome P450 enzyme system is capable of binding and metabolising formosanin c which is shown to bind the type II site (oxygen binding site) of the enzyme at the concentrations of 150 μM. The apparent binding constants (Ks) was 78μM. The observed effect of induction of phenobarbital on A max and V max suggests that several of the multiple forms of cytochrome P450 bind formosanin c. The incubation of Formosanin c with hepatic microsomes of rats in the presense of an NADPH-generating system led to decrease of cytochrome P-450 measured by its carbon monoxide difference spectra, and the decrease was enhanced by phenobarbital treatment.

並列關鍵字

Paris formosana Hayata ； PF-3 (Formosanin-c) ； Cytochrome P-450