Prevention of Myc‐Driven Prostate Cancer in Mice by Oral Administration of Sulforaphane

ABSTRACT Prevention is desirable to reduce suffering and death from prostate cancer. However, a clinical‐grade intervention for the prevention of this malignancy is still lacking. This study was undertaken to determine the feasibility of prostate cancer prevention by broccoli constituent sulforaphane (SFN) because epidemiological studies have suggested an inverse association between intake of broccoli and the risk of prostate cancer. Oral administration of 1 mg SFN/mouse (three times/week) to 5‐week‐old male Hi‐Myc transgenic mice for 5 weeks decreased the incidence of prostatic adenocarcinoma in situ by about 54% without causing weight loss or any other side effects. Existing literature strongly implicates fatty acid synthesis in prostate cancer progression. Therefore, we determined the effect of SFN treatment on fatty acid synthesis. Prostate cancer prevention by SFN in Hi‐Myc mice was accompanied by a decrease in: (a) the uptake of 11 C‐acetate in the prostate of live mice; (b) plasma levels of fatty acid synthesis intermediates acetyl‐CoA and malonyl‐CoA; (c) circulating levels of total free fatty acids (TFFA); (d) downregulation of fatty acid synthesis enzyme proteins acetyl‐CoA carboxylase 1 and fatty acid synthase; and (e) plasma levels of interkeukin‐10 and interleukin‐12. Because prostate cancer in Hi‐Myc mice is driven by Myc, we determined the effect of overexpression of c‐Myc in 22Rv1 cells on TFFA level. Overexpression of c‐Myc conferred partial protection against TFFA suppression by SFN treatment. In summary, this study reveals that SFN administration prevents prostate cancer development in Hi‐Myc mice by suppressing fatty acid synthesis.