In previous studies, we reported that
indole-3-carbinol (I3C) and myo-
inositol (MI) inhibit lung
adenoma induced by tobacco
smoke carcinogens in A/J mice. In this paper, we extended our work and examined the effects of I3C (70 or 30 micromol/g diet) and MI (56 micromol/g diet) against
vinyl carbamate (VC)-induced
lung adenocarcinoma by administering the agents from 1 week after the second of two
injections of VC until termination of the study at week 18. The higher dose of I3C decreased multiplicities of
tumors on the surface of the lung (26%, P = 0.0005),
carcinoma incidence (38%), multiplicity (67%, P < 0.0001) and size (complete abolition of
carcinoma with an area of >1.0 cm(2)) as well as
adenoma with cellular pleomorphism (46%, P < 0.0001). The lower dose of I3C was less effective. MI decreased multiplicities of pulmonary surface
tumors (20%, P = 0.0005),
adenoma with cellular pleomorphism (40%, P < 0.0001) and lung
adenoma (52%, P < 0.0001) and the proportion of the biggest
carcinoma (
carcinoma with an area of >1.0 cm(2), P < 0.05). Immunoblot analyses of lung tissues for potential target identification showed that I3C (70 micromol/g diet) inhibits
IkappaBalpha degradation,
nuclear factor-kappaB activation, expression of
cyclooxygenase-2, phospho-Akt and
fatty acid synthase (FAS) and activates
caspase-3 and
poly ADP ribose polymerase cleavage. The effect of MI was limited to inhibition of phospho-Akt and FAS expression. Our data show that I3C and MI inhibit lung
carcinoma and provide a basis for future evaluation of these compounds in clinical trials as chemopreventive agents for current and former smokers.