Indole-3-carbinol inhibited tobacco smoke carcinogen-induced lung adenocarcinoma in A/J mice when administered during the post-initiation or progression phase of lung tumorigenesis

We studied the chemopreventive efficacy of indole-3-carbinol (I3C), a phytochemical found in cruciferous vegetables, to inhibit tobacco carcinogen-induced lung adenocarcinoma in A/J mice when given following post-initiation or progression protocol. Moreover, we assessed the potential mechanisms responsible for the anticancer effects of I3C. Post-initiation administration of I3C decreased the multiplicity of surface tumors as well as all forms of histopathological lesions, including adenocarcinoma, whereas administration of the compound during tumor progression failed to decrease the multiplicity of surface tumors and early forms of microscopic lesions but reduced the frequency of adenocarcinoma. Mechanistic studies in A549 lung adenocarcinoma cells indicated that the lung cancer preventive effects of I3C are mediated, at least in part, via modulation of the receptor tyrosine kinase/PI3K/Akt signaling pathway.

► Indole-3-carbinol (I3C) prevents tobacco carcinogen-induced lung cancer in mice.
► Post-initiation administration of I3C decreased lung tumor number and size.
► Late stage treatment with I3C reduced tumor size only.
► Efficacy on lung cancer was higher when I3C was given in the post-initiation phase.
► Inhibition of the PI3K/Akt signaling pathway is the principal mode of action of I3C.