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

Fatty acid synthesis pathway is a valid target for 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 inhibition of prostate adenocarcinoma burden by about 61% that was accompanied by a significant decrease in prostate tumor levels of c-Myc and PCNA proteins and increased apoptosis. Expression of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN) were lower by about 46% and 31%, respectively, in the prostate tumor of SFN-treated mice when compared to 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 group (n= 19) or placebo group (n= 22). Patients were treated with 4 capsules BMAX or 4 capsules of matching placebo orally two times daily after breakfast and dinner for 4 weeks. Prostate tumor expression of c-Myc, ACC1, FASN, and Ki-67 proteins were significantly lower in the BMAX arm when compared to PBO group. However, serum or prostate tumor level of acetyl-CoA or TFFA was not decreased by BMAX treatment. A longer duration treatment with BMAX in early-stage prostate cancer patients may be necessary to lower circulating or prostate tumor level of TFFA.