Human metabolism of the experimental cancer therapeutic agent d-limonene

d-Limonene has efficacy in preclinical models of breast cancer, causing > 80% of carcinomas to regress with little host toxicity. We performed a pilot study on healthy human volunteers to identify plasma metabolites of limonene and to assess the toxicity of supradietary quantities of d-limonene....

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Veröffentlicht in:Cancer chemotherapy and pharmacology 1994-01, Vol.35 (1), p.31-37
Hauptverfasser: CROWELL, P. L, ELSON, C. E, BAILEY, H. H, ELEGBEDE, A, HAAG, J. D, GOULD, M. N
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container_end_page 37
container_issue 1
container_start_page 31
container_title Cancer chemotherapy and pharmacology
container_volume 35
creator CROWELL, P. L
ELSON, C. E
BAILEY, H. H
ELEGBEDE, A
HAAG, J. D
GOULD, M. N
description d-Limonene has efficacy in preclinical models of breast cancer, causing > 80% of carcinomas to regress with little host toxicity. We performed a pilot study on healthy human volunteers to identify plasma metabolites of limonene and to assess the toxicity of supradietary quantities of d-limonene. Seven subjects ingested 100 mg/kg limonene in a custard. Blood was drawn at 0 and 24 h for chemistry-panel analysis and at 0, 4, and 24 h for limonene-metabolite analysis. On-line capillary gas chromatography/mass spectrometry (GC/MS) analysis indicated that at least five compounds were present at 4 h that were not present at time zero. Two major peaks were identified as the rat limonene metabolites dihydroperillic acid and perillic acid, and two minor peaks were found to be the respective methyl esters of these acids. A third major peak was identified as limonene-1,2-diol. Limonene was a minor component. At a dose of 100 mg/kg, limonene caused no gradable toxicity. Limonene is metabolized by humans and rats in a similar manner. These observations and the high therapeutic ratio of limonene in the chemotherapy of rodent cancers suggest that limonene may be an efficacious chemotherapeutic agent for human malignancies.
doi_str_mv 10.1007/BF00686281
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source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Adult
Antineoplastic agents
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - blood
Antineoplastic Agents, Phytogenic - pharmacokinetics
Biological and medical sciences
Cyclohexenes
Female
Gas Chromatography-Mass Spectrometry
General aspects
Humans
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Pilot Projects
Reference Values
Terpenes - administration & dosage
Terpenes - blood
Terpenes - pharmacokinetics
title Human metabolism of the experimental cancer therapeutic agent d-limonene
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