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Updated: Mar 11, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Restoration of Immune Surveillance in Prostate Cancer Prevention by Sulforaphane in Hi-Myc Mice
Krishna B Singh1, Eun-Ryeong Hahm1, Joshi J Alumkal2
1Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Abstract:
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.
Insights
Sulforaphane (SFN), a broccoli compound, restores immune surveillance in a prostate cancer mouse model by increasing CD8+ T cells and dendritic cells. SFN also reduced immunosuppressive cells and inflammatory cytokines, suggesting a role in cancer prevention.
Area of Science:
- Oncology
- Immunology
- Nutritional Science
Background:
- Sulforaphane (SFN) is a broccoli constituent with demonstrated preclinical efficacy in preventing prostate cancer.
- The precise mechanisms by which SFN exerts its chemopreventive effects, particularly regarding immune modulation, remain incompletely understood.
Purpose of the Study:
- To investigate the impact of oral SFN administration on immune surveillance in a relevant prostate cancer mouse model (Hi-Myc mice).
- To elucidate the immunomodulatory effects of SFN in the context of prostate cancer development and progression.
Main Methods:
- Hi-Myc mice were treated with SFN orally for 16 weeks.
- Flow cytometry was used to quantify immune cell populations (CD8+ T cells, CD4+ T cells, dendritic cells, NK cells, myeloid-derived suppressor cells) within prostate tumors.
- Plasma levels of various cytokines and chemokines were measured.
- In vitro studies assessed the effect of SFN on cancer cell proliferation with and without cytokine supplementation.
Main Results:
- SFN treatment significantly increased prostate tumor-infiltrating CD8+ T cells (1.33-fold) and dendritic cells (57%).
- SFN administration led to a significant decrease (approximately 30%) in myeloid-derived suppressor cells within prostate tumors.
- Plasma levels of several pro-inflammatory cytokines (e.g., IL-1β, IL-4) were significantly reduced in SFN-treated mice.
- SFN's in vitro inhibition of cancer cell proliferation was partially reversed by IL-4 and IL-13.
Conclusions:
- Oral SFN administration restores immune surveillance in the Hi-Myc mouse model of prostate cancer.
- SFN modulates the tumor immune microenvironment by enhancing anti-tumor immunity and reducing immunosuppression.
- These findings support the potential of SFN as a dietary intervention for prostate cancer prevention through immune system modulation.
