Restoration of Immune Surveillance in Prostate Cancer Prevention by Sulforaphane in Hi-Myc Mice.

Oral administration of broccoli constituent sulforaphane (SFN) prevents prostate cancer development in preclinical mouse models. However, the mechanism(s) underlying prostate cancer prevention by SFN are not fully understood. In this study, we used a human relevant mouse model (Hi-Myc mice) to demonstrate restoration of immune surveillance by oral SFN administration. Treatment of Hi-Myc mice with SFN for 16 weeks resulted in about 1.33-fold increase in the number of prostate tumor-infiltrating CD8α + T cells (p = 0.02 by Student's t-test). The number of CD4+ helper T cells was not affected by SFN treatment. The number of CD11c/MHCII+ dendritic cells was increased by about 57% upon SFN administration. On the other hand, the number of NKp46+ natural killer cells was not significantly affected by SFN treatment. Oral administration of SFN resulted in about 30% decrease in the number of Gr1/CD11b+ myeloid-derived suppressor cells in the prostate tumor when compared to control mice. Plasma levels of interleukin (IL)-1α, IL-1β, IL-4, IL-5, IL-10, and C-X-C motif chemokine ligand 2 (CXCL2 or MIP-2) were statistically significantly lower in SFN-treated mice when compared to control mice. Treatment of recurrent prostate cancer patients with 200 μmol/day of SFN-rich broccoli sprout extract for 20 weeks also caused a statistically significant decrease in plasma levels of IL-1β, IL-4, and IL-13. Cell proliferation inhibition by SFN in vitro was partially but significantly attenuated by IL-4 and IL-13 supplementation in 22Rv1 cells. These results indicate restoration of immune surveillance by oral SFN treatment in Hi-Myc mouse model.