Abstract
Background: Human cytochrome P450 2J2, an enzyme highly expressed in human extrahepatic tissues, is responsible for the biotransformation of xenobiotics including astemizole and ebastine. CYP2J2 is also overexpressed in various human tumor tissues and cancer cell lines and may present a potential target for therapy of human cancer. Objective: In this study, six tamoxifen analogues were screened as potential CYP2J2 enzyme inhibitors in human liver microsomes using a high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS). Results: Six compounds tested, 4-hydroxytoremifene, the active metabolite of toremifene, showed inhibitory potential against CYP2J2-catalyzed astemizole O-demethylation activity (IC 50 = 8.4 □M) in a dose-dependent manner. Conclusion: We suggest that 4-hydroxytoremifene might be a potential candidate for further evaluation for anticancer activity.
| Original language | English |
|---|---|
| Pages (from-to) | 77-82 |
| Number of pages | 6 |
| Journal | Advances in Environmental Biology |
| Volume | 9 |
| Issue number | 19 |
| State | Published - 1 Aug 2015 |
Keywords
- CYP2J2 human liver microsomes
- Hydroxytoremifene
- Inhibition mass spectrometry
