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Combinations of N-Acetyl-S-(N-2-Phenethylthiocarbamoyl)-L-Cysteine and myo-Inositol Inhibit Tobacco Carcinogen–Induced Lung Adenocarcinoma in Mice

Authors' Affiliation: University of Minnesota Cancer Center, Minneapolis, Minnesota

Requests for reprints: Fekadu Kassie, University of Minnesota Cancer Center, Mayo Mail Code 806, 420 Delaware Street Southeast, Minneapolis, MN 55455. Phone: 612-626-5143; Fax: 612-626-5135; E-mail: kassi012{at}umn.edu.

We have previously generated convincing evidence that combinations of N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine (PEITC-NAC; 3 µmol/g diet) and myo-inositol (MI; 56 µmol/g diet) were significantly more effective than the individual compounds as inhibitors of tobacco smoke carcinogen–induced lung tumorigenesis in A/J mice. In this study, we further investigated the efficacy of combinations of PEITC-NAC (9 or 15 µmol/g diet) and MI (56 µmol/g diet). Female A/J mice were treated with a mixture of the tobacco smoke carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene by gavage once weekly for 8 weeks. PEITC-NAC plus MI was given in the diet beginning at 1 day after the 4th of eight carcinogen treatments (temporal sequence A) or 1 week after the last carcinogen treatment (temporal sequence B). Regardless of the dose of carcinogen or PEITC-NAC plus MI, or temporal sequence, administration of PEITC-NAC plus MI significantly reduced the multiplicity of gross tumors and, in most instances, adenocarcinoma. PEITC-NAC plus MI was particularly effective against bigger tumors. The observed inhibition of lung tumorigenesis by PEITC-NAC plus MI was attributed, at least partly, to inhibition of cell proliferation and induction of apoptosis. These results clearly show the efficacy of PEITC-NAC plus MI in the prevention of tobacco carcinogen–induced lung adenocarcinoma in A/J mice and provide a basis for future evaluation of PEITC-NAC plus MI in clinical trials as a chemopreventive agent for current and former smokers.

Key Words: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone • benzo[a]pyrene • lung tumorigenesis • chemoprevention • N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine • myo-inositol

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