Carcinogenesis, Vol. 23, No. 9, 1455-1461,
September 2002
© 2002 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Inhibition of lung tumorigenesis in A/J mice by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine and myo-inositol, individually and in combination
University of Minnesota Cancer Center, Minneapolis, MN 55455, USA
Isothiocyanates, their N-acetylcysteine conjugates, and myo-inositol (MI) are inhibitors of lung tumorigenesis in A/J mice. However, chemoprevention by combinations of these compounds in different temporal sequences has not been examined. This is important for developing practical approaches to lung cancer chemoprevention in smokers and ex-smokers. We used a tumor model in which A/J mice are treated with 8 weekly doses of benzo[a]pyrene (B[a]P) plus 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and killed 19 weeks after the final treatment. In Experiment 1, isothiocyanates or their N-acetylcysteine conjugates were added to the diet (1 or 3 µmol/g) from 1 week before until 1 week after carcinogen treatment. The compounds were 2-phenethyl isothiocyanate (PEITC), 3-phenylpropyl isothiocyanate (PPITC), N-acetyl-S-(N-benzyl-thiocarbamoyl)-L-cysteine (BITC-NAC), N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine (PEITC-NAC), and N-acetyl-S-(N-3-phenylpropylthiocarbamoyl)-L-cysteine (PPITC-NAC). Significant reductions in lung tumor multiplicity were observed in mice treated with PEITC, PEITC-NAC, PPITC and PPITC-NAC. PEITC-NAC was chosen for combination studies with MI (Experiment 2). Mice were treated with B[a]P plus NNK without or with PEITC-NAC (3 µmol/g diet), MI (55.5 µmol/g diet), or PEITC-NAC plus MI (3 µmol plus 55.5 µmol/g diet). Different temporal sequences of dietary additions were investigated: carcinogen treatment phase; post-carcinogen treatment phase; entire experiment; 50% of carcinogen treatment phase until termination; and 75% of carcinogen treatment phase until termination. All treatments reduced lung tumor multiplicity except PEITC-NAC post-carcinogen or from 75% of the carcinogen treatment phase. Reduction of lung tumor multiplicity by PEITC-NAC plus MI was greater than that in the mice treated with the agents alone in all temporal sequences. When all results were combined, PEITC-NAC plus MI was significantly more effective than the agents alone. There was a significant trend for reduction in lung tumor multiplicity with increased duration of treatment by the chemopreventive agents. These results provide a basis for further development of mixtures of PEITC-NAC and MI for chemoprevention of lung cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Han, J. J. Gills, R. M. Memmott, S. Lam, and P. A. Dennis The Chemopreventive Agent Myoinositol Inhibits Akt and Extracellular Signal-Regulated Kinase in Bronchial Lesions from Heavy Smokers Cancer Prevention Research, April 1, 2009; 2(4): 370 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Johnson, F. Kassie, M. G. O'Sullivan, M. Negia, T. E. Hanson, P. Upadhyaya, P. P. Ruvolo, S. S. Hecht, and C. Xing Chemopreventive Effect of Kava on 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone plus Benzo[a]pyrene-Induced Lung Tumorigenesis in A/J Mice Cancer Prevention Research, November 1, 2008; 1(6): 430 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liao, D. N. Seril, A. L. Yang, G. G. Lu, and G.-Y. Yang Inhibition of chronic ulcerative colitis associated adenocarcinoma development in mice by inositol compounds Carcinogenesis, February 1, 2007; 28(2): 446 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Gupta, K. P. Miller, J. K. Babus, and J. A. Flaws Methoxychlor Inhibits Growth and Induces Atresia of Antral Follicles through an Oxidative Stress Pathway Toxicol. Sci., October 1, 2006; 93(2): 382 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lam, A. McWilliams, J. leRiche, C. MacAulay, L. Wattenberg, and E. Szabo A Phase I Study of myo-Inositol for Lung Cancer Chemoprevention. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1526 - 1531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.-S. Hwang and H. J. Lee Allyl Isothiocyanate and Its N-Acetylcysteine Conjugate Suppress Metastasis via Inhibition of Invasion, Migration, and Matrix Metalloproteinase-2/-9 Activities in SK-Hep1 Human Hepatoma Cells. Experimental Biology and Medicine, April 1, 2006; 231(4): 421 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Hecht Deguelin as a Chemopreventive Agent in Mouse Lung Tumorigenesis Induced by Tobacco Smoke Carcinogens J Natl Cancer Inst, November 16, 2005; 97(22): 1634 - 1635. [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Lee, S.-H. Oh, J. K. Woo, W.-Y. Kim, C. S. Van Pelt, R. E. Price, D. Cody, H. Tran, J. M. Pezzuto, R. M. Moriarty, et al. Chemopreventive Effects of Deguelin, a Novel Akt Inhibitor, on Tobacco-Induced Lung Tumorigenesis J Natl Cancer Inst, November 16, 2005; 97(22): 1695 - 1699. [Abstract] [Full Text] [PDF]
|
|