PMID- 29668854
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20220318
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 39
IP  - 6
DP  - 2018 May 28
TI  - Prostate cancer chemoprevention by sulforaphane in a preclinical mouse model is 
      associated with inhibition of fatty acid metabolism.
PG  - 826-837
LID - 10.1093/carcin/bgy051 [doi]
AB  - Increased de novo synthesis of fatty acids is a rather unique and targetable 
      mechanism of human prostate cancer. We have shown previously that oral 
      administration of sulforaphane (SFN) significantly inhibits the incidence and/or 
      burden of prostatic intraepithelial neoplasia and well-differentiated 
      adenocarcinoma in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. The 
      present study used cellular models of prostate cancer and archived 
      plasma/adenocarcinoma tissues and sections from the TRAMP study to demonstrate 
      inhibition of fatty acid synthesis by SFN treatment in vitro and in vivo. 
      Treatment of androgen-responsive (LNCaP) and castration-resistant (22Rv1) human 
      prostate cancer cells with SFN (5 and 10 muM) resulted in downregulation of 
      protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid 
      synthase (FASN), but not ATP citrate lyase. Protein and mRNA levels of carnitine 
      palmitoyltransferase 1A (CPT1A), which facilitates fatty acid uptake by 
      mitochondria for beta-oxidation, were also decreased following SFN treatment in both 
      cell lines. Immunohistochemistry revealed a significant decrease in expression of 
      FASN and ACC1 proteins in prostate adenocarcinoma sections of SFN-treated TRAMP 
      mice when compared with controls. SFN administration to TRAMP mice resulted in a 
      significant decrease in plasma and/or prostate adenocarcinoma levels of total 
      free fatty acids, total phospholipids, acetyl-CoA and ATP. Consistent with these 
      results, number of neutral lipid droplets was lower in the prostate 
      adenocarcinoma sections of SFN-treated TRAMP mice than in control tumors. 
      Collectively, these observations indicate that prostate cancer chemoprevention by 
      SFN in TRAMP mice is associated with inhibition of fatty acid metabolism.
FAU - Singh, Krishna B
AU  - Singh KB
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, Pittsburgh, PA, USA.
FAU - Kim, Su-Hyeong
AU  - Kim SH
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, Pittsburgh, PA, USA.
FAU - Hahm, Eun-Ryeong
AU  - Hahm ER
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, Pittsburgh, PA, USA.
FAU - Pore, Subrata K
AU  - Pore SK
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, Pittsburgh, PA, USA.
FAU - Jacobs, Bruce L
AU  - Jacobs BL
AD  - Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, 
      PA, USA.
FAU - Singh, Shivendra V
AU  - Singh SV
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine, Pittsburgh, PA, USA.
AD  - UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA, USA.
LA  - eng
GR  - R01 CA101753/CA/NCI NIH HHS/United States
GR  - R01 CA115498/CA/NCI NIH HHS/United States
GR  - P30 CA047904/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Fatty Acids)
RN  - 0 (Isothiocyanates)
RN  - 0 (Sulfoxides)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Adenocarcinoma/metabolism/prevention & control
MH  - Animals
MH  - Anticarcinogenic Agents/*pharmacology
MH  - Chemoprevention/methods
MH  - Fatty Acid Synthases/drug effects/metabolism
MH  - Fatty Acids/*metabolism
MH  - Humans
MH  - Isothiocyanates/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Prostate/drug effects/metabolism
MH  - Prostatic Intraepithelial Neoplasia/metabolism/prevention & control
MH  - Prostatic Neoplasms/metabolism/*prevention & control
MH  - Sulfoxides
PMC - PMC5972626
EDAT- 2018/04/19 06:00
MHDA- 2019/01/29 06:00
PMCR- 2019/05/28
CRDT- 2018/04/19 06:00
PHST- 2017/08/22 00:00 [received]
PHST- 2018/04/10 00:00 [accepted]
PHST- 2018/04/19 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
PHST- 2018/04/19 06:00 [entrez]
PHST- 2019/05/28 00:00 [pmc-release]
AID - 4969927 [pii]
AID - bgy051 [pii]
AID - 10.1093/carcin/bgy051 [doi]
PST - ppublish
SO  - Carcinogenesis. 2018 May 28;39(6):826-837. doi: 10.1093/carcin/bgy051.