PMID- 36327818
OWN - NLM
STAT- MEDLINE
DCOM- 20221206
LR  - 20221206
IS  - 1618-0631 (Electronic)
IS  - 0344-0338 (Linking)
VI  - 240
DP  - 2022 Dec
TI  - Androgens and low density lipoprotein-cholesterol interplay in modulating 
      prostate cancer cell fate and metabolism.
PG  - 154181
LID - S0344-0338(22)00425-3 [pii]
LID - 10.1016/j.prp.2022.154181 [doi]
AB  - BACKGROUND: Androgens, the known drivers of prostate cancer (PCa), have been 
      indicated as important metabolic regulators with a relevant role in stimulating 
      lipid metabolism. Also, the relationship between obesity and the aggressiveness 
      of PCa has been established. However, it is unknown if the androgenic hormonal 
      environment may alter the response of PCa cells to lipid availability. PURPOSE: 
      The present study evaluated the effect of 5alpha-dihydrotestosterone (DHT) in 
      regulating lipid metabolism, and the interplay between this hormone and 
      low-density lipoprotein (LDL)-cholesterol in modulating PCa cells fate. METHODS: 
      Non-neoplastic and neoplastic PCa cells were treated with 10 nM DHT, and the 
      expression of fatty acids transporter, fatty acid synthase (FASN), and carnitine 
      palmitoyltransferase 1A (CPT1A) evaluated. PCa cells were also exposed to LDL 
      (100 mug/ml) in the presence or absence of DHT. RESULTS: Treatment with DHT 
      upregulated the expression of FASN and CPT1A in androgen-sensitive PCa cells. In 
      contrast, LDL supplementation suppressed FASN expression regardless of the 
      presence of DHT, whereas augmenting CPT1A levels. Our results also showed that 
      LDL-cholesterol increased PCa cells viability, proliferation, and migration 
      dependently on the presence of DHT. Moreover, LDL and DHT synergistically 
      enhanced the accumulation of lipid droplets in PCa cells. CONCLUSIONS: The 
      obtained results show that androgens deregulate lipid metabolism and enhance the 
      effects of LDL increasing PCa cells viability, proliferation and migration. The 
      present findings support clinical data linking obesity with PCa and first 
      implicate androgens in this relationship. Also, they sustain the application of 
      pharmacological approaches targeting cholesterol availability and androgens 
      signaling simultaneously.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.
FAU - Cardoso, Henrique J
AU  - Cardoso HJ
AD  - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 
      Covilha, Portugal.
FAU - Figueira, Marilia I
AU  - Figueira MI
AD  - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 
      Covilha, Portugal.
FAU - Carvalho, Tiago M A
AU  - Carvalho TMA
AD  - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 
      Covilha, Portugal.
FAU - Serra, Catarina D M
AU  - Serra CDM
AD  - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 
      Covilha, Portugal.
FAU - Vaz, Catia V
AU  - Vaz CV
AD  - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 
      Covilha, Portugal.
FAU - Madureira, Patricia A
AU  - Madureira PA
AD  - Brain Tumour Research Centre of Excellence, Institute of Biomedical and 
      Biomolecular Sciences, University of Portsmouth, Portsmouth, United Kingdom; 
      Centre for Biomedical Research (CBMR), Campus of Gambelas, University of Algarve, 
      Faro, Portugal.
FAU - Socorro, Silvia
AU  - Socorro S
AD  - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 
      Covilha, Portugal. Electronic address: ssocorro@fcsaude.ubi.pt.
LA  - eng
PT  - Journal Article
DEP - 20221022
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
RN  - 0 (Androgens)
RN  - 0 (Cholesterol, LDL)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Androgens/pharmacology
MH  - Cholesterol, LDL/therapeutic use
MH  - *Prostatic Neoplasms/metabolism
MH  - Dihydrotestosterone/pharmacology
MH  - Obesity
MH  - Receptors, Androgen/metabolism
OTO - NOTNLM
OT  - Androgens
OT  - Fatty acid synthase
OT  - LDL-cholesterol
OT  - Lipid metabolism
OT  - Obesity
OT  - Prostate cancer
COIS- Declaration of Competing Interest The authors report no conflicts of interest.
EDAT- 2022/11/04 06:00
MHDA- 2022/12/07 06:00
CRDT- 2022/11/03 19:30
PHST- 2022/07/28 00:00 [received]
PHST- 2022/10/16 00:00 [accepted]
PHST- 2022/11/04 06:00 [pubmed]
PHST- 2022/12/07 06:00 [medline]
PHST- 2022/11/03 19:30 [entrez]
AID - S0344-0338(22)00425-3 [pii]
AID - 10.1016/j.prp.2022.154181 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2022 Dec;240:154181. doi: 10.1016/j.prp.2022.154181. Epub 2022 
      Oct 22.