Combinations of N-Acetyl-S-(N-2-Phenethylthiocarbamoyl)-L-Cysteine and myo-inositol inhibit tobacco carcinogen-induced lung adenocarcinoma in mice.
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.
Kassie
Fekadu
F
University of Minnesota Cancer Center, Mayo Mail Code 806, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA. kassi012@umn.edu
Matise
Ilze
I
Negia
Mesfin
M
Lahti
David
D
Pan
Yunqian
Y
Scherber
Robyn
R
Upadhyaya
Pramod
P
Hecht
Stephen S
SS
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004353:Drug Evaluation, Preclinical; D005260:Female; D007294:Inositol / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008954:Models, Biological; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011897:Random Allocation; D012907:Smoking / Q000009:adverse effects; D013859:Thiocarbamates / Q000008:administration & dosage*; D051025:bcl-Associated Death Protein / Q000378:metabolism
C494820:Bad protein, mouse; D002273:Carcinogens; C465294:N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine; D013859:Thiocarbamates; D051025:bcl-Associated Death Protein; D007294:Inositol; D011065:Poly(ADP-ribose) Polymerases; D051058:Oncogene Protein v-akt; D003545:Cysteine