PMID- 32670813
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201007
IS  - 2225-4110 (Print)
IS  - 2225-4110 (Electronic)
IS  - 2225-4110 (Linking)
VI  - 10
IP  - 3
DP  - 2020 May
TI  - Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer 
      cells.
PG  - 188-197
LID - 10.1016/j.jtcme.2020.02.002 [doi]
AB  - Prior research argues for a role of increased de novo fatty acid synthesis in 
      pathogenesis of prostate adenocarcinoma, which remains a leading cause of 
      cancer-associated mortality in American men. A safe and effective inhibitor of 
      fatty acid synthesis is still a clinically unmet need. Herein, we investigated 
      the effect of ethanol extract of Withania somnifera root (WRE) standardized for 
      one of its components (withaferin A) on fatty acid synthesis using LNCaP and 
      22Rv1 human prostate cancer cells. Withania somnifera is a medicinal plant used 
      in the Ayurvedic medicine practiced in India. Western blotting and confocal 
      microscopy revealed a statistically significant decrease in protein levels of key 
      fatty acid metabolism enzymes including ATP citrate lyase (ACLY), acetyl-CoA 
      carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine 
      palmitoyltransferase 1A (CPT1A) in WRE-treated cells compared with solvent 
      control. The mRNA levels of ACLY, ACC1, FASN, and CPT1A were also lower in 
      WRE-treated cells in comparison with control. Consequently, WRE treatment 
      resulted in a significant decrease in intracellular levels of acetyl-CoA, total 
      free fatty acids, and neutral lipid droplets in both LNCaP and 22Rv1 cells. WRE 
      exhibited greater potency for fatty acid synthesis inhibition at equimolar 
      concentration than cerulenin and etomoxir. Exposure to WRE results in 
      downregulation of c-Myc and p-Akt(S473) proteins in 22Rv1 cell line. However, 
      overexpression of only c-Myc conferred protection against clonogenic cell 
      survival and lipogenesis inhibition by WRE. In conclusion, these results indicate 
      that WRE is a novel inhibitor of fatty acid synthesis in human prostate cancer 
      cells.
CI  - (c) 2020 Center for Food and Biomolecules, National Taiwan University. Production 
      and hosting by Elsevier Taiwan LLC.
FAU - Kim, Su-Hyeong
AU  - Kim SH
AD  - Department of Pharmacology & Chemical Biology, University of Pittsburgh School of 
      Medicine, Pittsburgh, PA, USA.
FAU - Singh, Krishna B
AU  - Singh KB
AD  - Department of Pharmacology & Chemical Biology, University of Pittsburgh School of 
      Medicine, Pittsburgh, PA, USA.
FAU - Hahm, Eun-Ryeong
AU  - Hahm ER
AD  - Department of Pharmacology & Chemical Biology, University of Pittsburgh School of 
      Medicine, Pittsburgh, PA, USA.
FAU - Lokeshwar, Balakrishna L
AU  - Lokeshwar BL
AD  - Georgia Cancer Center and Department of Medicine, Augusta University, Augusta, 
      GA, USA.
FAU - Singh, Shivendra V
AU  - Singh SV
AD  - Department of Pharmacology & 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 CA142604/CA/NCI NIH HHS/United States
GR  - R01 CA225716/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20200207
PL  - Netherlands
TA  - J Tradit Complement Med
JT  - Journal of traditional and complementary medicine
JID - 101605474
PMC - PMC7340880
OTO - NOTNLM
OT  - ACC1, acetyl-CoA carboxylase 1
OT  - ACLY, ATP citrate lyase
OT  - ANOVA, one-way analysis of variance
OT  - ATP citrate lyase
OT  - Acetyl-CoA carboxylase 1
OT  - CPT1A, carnitine palmitoyltransferase 1A
OT  - CTCF, corrected total cell fluorescence
OT  - Cer, cerulenin
OT  - Chemoprevention
OT  - Eto, etomoxir
OT  - FASN, fatty acid synthase
OT  - Fatty acid synthase
OT  - GAPDH, glyceraldehyde 3-phosphate dehydrogenase
OT  - Prostate cancer
OT  - Vec, pcDNA3 empty vector transfected cells
OT  - WRE, Withania somnifera root extract
OT  - caAkt, constitutively active Akt
OT  - qRT-PCR, quantitative reverse transcription-polymerase chain reaction
COIS- None of the authors has any conflict of interest.
EDAT- 2020/07/17 06:00
MHDA- 2020/07/17 06:01
PMCR- 2020/02/07
CRDT- 2020/07/17 06:00
PHST- 2020/01/05 00:00 [received]
PHST- 2020/02/04 00:00 [revised]
PHST- 2020/02/05 00:00 [accepted]
PHST- 2020/07/17 06:00 [entrez]
PHST- 2020/07/17 06:00 [pubmed]
PHST- 2020/07/17 06:01 [medline]
PHST- 2020/02/07 00:00 [pmc-release]
AID - S2225-4110(20)30015-8 [pii]
AID - 10.1016/j.jtcme.2020.02.002 [doi]
PST - epublish
SO  - J Tradit Complement Med. 2020 Feb 7;10(3):188-197. doi: 
      10.1016/j.jtcme.2020.02.002. eCollection 2020 May.