Increased de novo synthesis of
fatty acids is a distinctive feature of
prostate cancer, which continues to be a leading cause of
cancer-related deaths among American men. Therefore, inhibition of de novo
fatty acid synthesis represents an attractive strategy for
chemoprevention of
prostate cancer. We have shown previously that dietary feeding of
phenethyl isothiocyanate (
PEITC), a
phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly differentiated
prostate cancer in transgenic
adenocarcinoma of mouse prostate (TRAMP) model. The current study was designed to test the hypothesis of whether
fatty acid intermediate(s) can serve as noninvasive
biomarker(s) of
prostate cancer chemoprevention by
PEITC using archived plasma and
tumor specimens from the TRAMP study as well as cellular models of
prostate cancer. Exposure of
prostate cancer cells (LNCaP and 22Rv1) to pharmacologic concentrations of
PEITC resulted in downregulation of key
fatty acid metabolism
proteins, including
acetyl-CoA carboxylase 1 (ACC1),
fatty acid synthase (FASN), and
carnitine palmitoyltransferase 1A (CPT1A). The
mRNA expression of FASN and CPT1A as well as
acetyl-CoA levels were decreased by
PEITC treatment in both cell lines.
PEITC administration to TRAMP mice also resulted in a significant decrease in
tumor expression of FASN
protein. Consistent with these findings, the levels of total
free fatty acids, total
phospholipids,
triglyceride, and
ATP were significantly lower in the plasma and/or prostate
tumors of
PEITC-treated TRAMP mice compared with controls. The current study is the first to implicate inhibition of
fatty acid synthesis in
prostate cancer chemoprevention by
PEITC.
Cancer Prev Res; 10(5); 279-89. ©2017 AACR.