Bench-to-Bedside Evaluation of Sulforaphane/BroccoMax on Fatty Acid Synthesis in Prostate Cancer

The fatty acid synthesis pathway is a valid target for the prevention of prostate cancer. However, a clinical-grade inhibitor of fatty acid synthesis is still lacking. This bench-to-bedside study was undertaken to determine the feasibility of fatty acid synthesis inhibition using broccoli constituent sulforaphane (SFN) and its clinical-grade formulation BroccoMax (BMAX). Oral administration of SFN to Hi-Myc mice resulted in the inhibition of prostate adenocarcinoma burden by about 61% that was accompanied by a significant decrease in prostate tumor levels of c-Myc and proliferating cell nuclear antigen proteins and increased apoptosis. Expression of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN) was lower by about 46% and 31%, respectively, in the prostate tumor of SFN-treated mice when compared with that of control mice (P < 0.001). Plasma levels of total free fatty acids (TFFA), cholesterol, and total phospholipids were decreased significantly following SFN treatment. In a double-blind clinical trial, patients with histologically confirmed prostate cancer were randomized to the BMAX (n = 19) or placebo (PBO) group (n = 22). Patients were treated with four capsules of BMAX or four capsules of matching PBO orally two times daily after breakfast and dinner for 4 weeks. Prostate tumor expression of c-Myc, ACC1, FASN, and Ki-67 proteins was significantly lower in the BMAX arm when compared with the PBO group. However, the serum or prostate tumor level of acetyl-CoA or TFFA was not decreased by BMAX treatment. A longer duration treatment with BMAX in patients with early-stage prostate cancer may be necessary to lower the circulating or prostate tumor level of TFFA.

Fatty acid synthesis is a valid target for the prevention of human prostate cancer. In this study, we determined the feasibility of fatty acid synthesis inhibition using SFN in a mouse model and BMAX, its clinical-grade formulation, in prostatectomy patients.