PMID- 28292742
OWN - NLM
STAT- MEDLINE
DCOM- 20180302
LR  - 20220316
IS  - 1940-6215 (Electronic)
IS  - 1940-6207 (Print)
IS  - 1940-6215 (Linking)
VI  - 10
IP  - 5
DP  - 2017 May
TI  - Fatty Acid Synthesis Intermediates Represent Novel Noninvasive Biomarkers of 
      Prostate Cancer Chemoprevention by Phenethyl Isothiocyanate.
PG  - 279-289
LID - 10.1158/1940-6207.CAPR-17-0001 [doi]
AB  - 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. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Singh, Krishna B
AU  - Singh KB
AD  - Department of Pharmacology & Chemical Biology, and University of Pittsburgh 
      Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, 
      Pennsylvania.
FAU - Singh, Shivendra V
AU  - Singh SV
AD  - Department of Pharmacology & Chemical Biology, and University of Pittsburgh 
      Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, 
      Pennsylvania. singhs@upmc.edu.
LA  - eng
GR  - P30 CA047904/CA/NCI NIH HHS/United States
GR  - R01 CA101753/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170314
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Fatty Acids)
RN  - 0 (Isothiocyanates)
RN  - 6U7TFK75KV (phenethyl isothiocyanate)
SB  - IM
MH  - Adenocarcinoma/*prevention & control
MH  - Animals
MH  - Anticarcinogenic Agents/*pharmacology
MH  - Biomarkers, Tumor/*analysis
MH  - Chemoprevention
MH  - Fatty Acids/*metabolism
MH  - Isothiocyanates/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Prostatic Neoplasms/*prevention & control
PMC - PMC5439500
MID - NIHMS863340
COIS- Conflict of Interest: None of the authors has any conflict of interest.
EDAT- 2017/03/16 06:00
MHDA- 2018/03/03 06:00
PMCR- 2018/05/01
CRDT- 2017/03/16 06:00
PHST- 2017/01/03 00:00 [received]
PHST- 2017/02/10 00:00 [revised]
PHST- 2017/03/10 00:00 [accepted]
PHST- 2017/03/16 06:00 [pubmed]
PHST- 2018/03/03 06:00 [medline]
PHST- 2017/03/16 06:00 [entrez]
PHST- 2018/05/01 00:00 [pmc-release]
AID - 1940-6207.CAPR-17-0001 [pii]
AID - 10.1158/1940-6207.CAPR-17-0001 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2017 May;10(5):279-289. doi: 
      10.1158/1940-6207.CAPR-17-0001. Epub 2017 Mar 14.