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.
Cancer prevention research (Philadelphia, Pa.). 2026 Mar 20 [Epub ahead of print]
Eun-Ryeong Hahm, Bruce L Jacobs, Krishna B Singh, Su-Hyeong Kim, Rahul A Parikh, Daniel P Normolle, Rajiv Dhir, Tunde Oyebamiji, Xuejiao Sun, Yang Liu, Leonard J Appleman, Stacy L Gelhaus, Shivendra V Singh
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania., Department of Medical Oncology, Kansas University Medical Center, Kansas City, Missouri., Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania., Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Biomedical Optical Imaging Laboratory, Departments of Medicine and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.