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.
Bibliographical noteFunding Information:
This study was funded by a research grant from NIH to FK (CA-128801). We thank Bob Carlson for help in the preparation of the Figures and Melissa Schutten, Josh Parker and Paula Overn, from Comparative Pathology Shared Resource, for help with the mouse necropsy, tumor count and histopathological and immunohistochemical analysis of mouse lung tissues.
- A549 cells
- Lung adenocarcinoma