Identification of metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth.

摘要: Limonene has been shown to be an effective, nontoxic chemopreventive and chemotherapeutic agent in chemically induced rat mammary-cancer models. The present study characterized circulating metabolites of limonene female rats determined their effects on cell growth. Metabolism was analyzed plasma extracts by gas chromatography. Rapid conversion two major detected. These comprised more than 80% the limonene-derived material at 1 h after administration thereafter, whereas itself accounted for only 15%. were mass spectroscopy infrared spectroscopy. probable structures synthesized, identities confirmed comparison retention times spectra. found perillic acid dihydroperillic acid. We have previously reported that limonene, acid, inhibit posttranslational isoprenylation p21ras other 21- 26-kDa cell-growth-associated proteins NIH3T3 cells mammary epithelial cells. In study, growth a dose-dependent manner. Thus, rat, are potent inhibitors protein is also inhibitor data raise possibility antitumor vivo may mediated via and, perhaps, metabolites.