Combinations of N-Acetyl-S-(N-2-Phenethylthiocarbamoyl)-L-Cysteine and myo-inositol inhibit tobacco carcinogen-induced lung adenocarcinoma in mice.

Abstract

We have previously generated convincing evidence that combinations of N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine (PEITC-NAC; 3 micromol/g diet) and myo-inositol (MI; 56 micromol/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 micromol/g diet) and MI (56 micromol/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.

• Authors: Fekadu Kassie, Ilze Matise, Mesfin Negia, David Lahti, Yunqian Pan, Robyn Scherber, Pramod Upadhyaya, Stephen S Hecht
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 1 Issue 4 Pg. 285-97 (Sep 2008) ISSN: 1940-6215 [Electronic] United States
• PMID: 19138972 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Bad protein, mouse
• Carcinogens
• N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine
• Thiocarbamates
• bcl-Associated Death Protein
• Inositol
• Poly(ADP-ribose) Polymerases
• Oncogene Protein v-akt
• Cysteine

Topics

• Adenocarcinoma (chemically induced, metabolism, pathology, prevention & control)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinogens (toxicity)
• Cell Proliferation (drug effects)
• Cysteine (administration & dosage, analogs & derivatives)
• Drug Evaluation, Preclinical
• Female
• Inositol (administration & dosage)
• Lung Neoplasms (chemically induced, metabolism, pathology, prevention & control)
• Mice
• Models, Biological
• Oncogene Protein v-akt (metabolism)
• Phosphorylation (drug effects)
• Poly(ADP-ribose) Polymerases (metabolism)
• Random Allocation
• Smoking (adverse effects)
• Thiocarbamates (administration & dosage)
• bcl-Associated Death Protein (metabolism)