D-Limonene in citrus fruit with anticarcinogenic action

H. Schmandke, Bergholz-Rehbrücke

D-limonene, a monoterpene, is a main component of the volatile oils of citrus-fruit peels. At temperatures not exceeding 50 °C limonene, if protected against light, is not susceptible to oxidation. High levels of limonene are contained in fresh Mediterranean-style lemonade (up to 1 g/l) and in commercial citrus juices (up to 85 mg/l).

Limonene is completely absorbed and extensively metabolized. About 24 h after intake, 70 % of the limonene ingested are renally excreted. As soon as 4 h after intake, only traces of limonene and its major metabolites perillic acid, dihydroperillic acid and limonene-1,2-diol, as well as traces of the methyl esters of these acids and of limonene-8,9-diol and iso-perillic acid are still present in the plasma. Maximum concentrations of limonene and its metabolites have been found in fatty, mammary and liver tissue. In the tumor tissue of patients with breast cancer, limonene levels were six times as high as those in the plasma. Major urinary metabolites are glycine and glucuronyl conjugates of the perillic acid isomers, dihydroperillic acid, limonene-6-ol (carveol), perillylalcohol and traces of limonene-8,9-diol (uroterpenol).

In vivo, limonene has preventive and therapeutic effects on chemically induced tumors of different rat and mouse tissues. At the same time isoprenylation of cell growth associated 21-26 kDa proteins and of the corresponding protein prenyltransferases are inhibited. This also applies to the 3-hydroxy-3-methyl glutaryl CoA reductase resulting in a decrease of farnesyl and geranylgeranyl pyrophosphate pools. Besides, the carcinogen-metabolizing liver enzymes glutathione-S transferase and uridin diphosphoglucuronosyl transferase are activated. In- vitro experiments in human cancer cells have shown that the limonene metabolites perillyl alcohol, perillic acid and limonene-1,2-diol, and not limonene itself, are most effective in inhibiting 21-26 kDa protein isoprenylation.

In preclinical studies in patients with advanced cancer the maximum tolerable oral dose applied for several month was 13.8 g limonene per day. In some cases tumor growth was inhibited.

Keywords: D-Limonene, citrus fruit, anticarcinogenic action

Sie finden den Artikel in deutscher Sprache in Ernährungs-Umschau 07/03 ab Seite 264.