Sulforaphane Inhibits Prostate Carcinogenesis and Pulmonary Metastasis in TRAMP Mice in Association with Increased Cytotoxicity of Natural Killer Cells

Abstract

The present study shows that oral gavage of 6 Mmol D,Lsulforaphane (SFN), a synthetic analogue of cruciferous vegetable-derived L isomer, thrice per week beginning at 6 weeks of age, significantly inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice without causing any side effects. The incidence of the prostatic intraepithelial neoplasia and well-differentiated (WD) carcinoma were f23% to 28% lower (P < 0.05 compared with control by MannWhitney test) in the dorsolateral prostate (DLP) of SFNtreated mice compared with controls, which was not due to the suppression of T-antigen expression. The area occupied by the WD carcinoma was also f44% lower in the DLP of SFNtreated mice relative to that of control mice (P = 0.0011 by Mann Whitney test). Strikingly, the SFN-treated mice exhibited f50% and 63% decrease, respectively, in pulmonary metastasis incidence and multiplicity compared with control mice (P < 0.05 by t test). The DLP from SFN-treated mice showed decreased cellular proliferation and increased apoptosis when compared with that from control mice. Additionally, SFN administration enhanced cytotoxicity of cocultures of natural killer (NK) cells and dendritic cells (DC) against TRAMP-C1 target cells, which correlated with infiltration of T cells in the neoplastic lesions and increased levels of interleukin-12 production by the DC. In conclusion, the results of the present study indicate that SFN administration inhibits prostate cancer progression and pulmonary metastasis in TRAMP mice by reducing cell proliferation and augmenting NK cell lytic activity.

Effect of NaCl treatments on glucosinolate metabolism in broccoli sprouts

“…Sulforaphane has been implicated in the cancerprotective effects of Brassica vegetables (Singh et al, 2009;Sharma et al, 2010). The accumulation of sulforaphane in 7-d-old sprouts treated with 100 mmol/L NaCl was 2.1 times of that in the control sprouts in the present study, suggesting that sprouts treated with high concentration of NaCl may be desirable from a health perspective.…”

Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activation of the Nrf2 transcription factor and selective cytotoxic activity

“…In this regard, animal studies on rats have established the chemopreventive activity of sulforaphane against colon cancer [12], and recent preclinical and clinical studies have confirmed the chemopreventive activity of sulforaphane in women at risk for breast cancer [13]. In addition to increasing cellular capacity for detoxifying electrophiles and oxidants, SFN has been shown to induce apoptosis, and to inhibit cell cycle progression and angiogenesis [14][15][16][17][18][19]. Most recently, SFN has also been shown to induce antiproliferative effects via epigenetic mechanisms [20], namely acting as dietary histone deacetylase inhibitor through its metabolite SFN-cysteine 3 [21,22], and to suppress DNA methylation [23].…”

Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6

“…Sulforaphane, a derivative of glucoraphanin found in crucifers, has heterogeneous biological activities including Phase 2 enzyme induction, cell cycle arrest, and apoptosis, but data on pathways that mediate effects on cell growth, survival, and differentiation are incomplete (5). Of note, several reports show that sulforaphane treatment of prostate cancer cells in vitro leads to reduced prostate cancer cell survival, and treatment of xenograft implants or transgenic animal models of prostate cancer with sulforaphane inhibits tumor formation and metastases (6)(7)(8).…”