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Cancer Prev Res (Phila). 2016 May;9(5):396-405. doi: 10.1158/1940-6207.CAPR-15-0380. Epub 2016 Mar 7.

Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers.

Author information

1
Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
2
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
3
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Department of Biochemistry, Molecular Biology and BioPhysics, University of Minnesota, Minneapolis, Minnesota.
4
Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
5
Department of Food Science and Nutrition, University of Minnesota, St. Paul, Minnesota.
6
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
7
Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California.
8
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. hecht002@umn.edu.

Abstract

2-Phenethyl isothiocyanate (PEITC), a natural product found as a conjugate in watercress and other cruciferous vegetables, is an inhibitor of the metabolic activation and lung carcinogenicity of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats and A/J mice. We carried out a clinical trial to determine whether PEITC also inhibits the metabolic activation of NNK in smokers. Cigarette smokers were recruited and asked to smoke cigarettes containing deuterium-labeled [pyridine-D4]NNK for an acclimation period of at least 1 week. Then subjects were randomly assigned to one of two arms: PEITC followed by placebo, or placebo followed by PEITC. During the 1-week treatment period, each subject took PEITC (10 mg in 1 mL of olive oil, 4 times per day). There was a 1-week washout period between the PEITC and placebo periods. The NNK metabolic activation ratio [pyridine-D4]hydroxy acid/total [pyridine-D4]NNAL was measured in urine samples to test the hypothesis that PEITC treatment modified NNK metabolism. Eighty-two smokers completed the study and were included in the analysis. Overall, the NNK metabolic activation ratio was reduced by 7.7% with PEITC treatment (P = 0.023). The results of this trial, while modest in effect size, provide a basis for further investigation of PEITC as an inhibitor of lung carcinogenesis by NNK in smokers. Cancer Prev Res; 9(5); 396-405.

PMID:
26951845
PMCID:
PMC4854759
DOI:
10.1158/1940-6207.CAPR-15-0380
[Indexed for MEDLINE]
Free PMC Article

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