PMID- 33647254
OWN - NLM
STAT- MEDLINE
DCOM- 20210519
LR  - 20210519
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 898
DP  - 2021 May 5
TI  - The in vitro effect of the diabetes-associated markers insulin, leptin and 
      oxidative stress on cellular characteristics promoting breast cancer progression 
      is GLUT1-dependent.
PG  - 173980
LID - S0014-2999(21)00133-3 [pii]
LID - 10.1016/j.ejphar.2021.173980 [doi]
AB  - Obesity and type 2 diabetes mellitus (T2DM) associate with increased incidence 
      and mortality from many cancers, including breast cancer. The mechanisms involved 
      in this relation remain poorly understood. Our study aimed to investigate the in 
      vitro effect of high levels of glucose, insulin, leptin, TNF-alpha, INF-gamma and 
      oxidative stress (induced with tert-butylhydroperoxide (TBH)), which are 
      associated with T2DM, upon glucose uptake by breast cancer (MCF-7 and MDA-MB-231) 
      and non-cancer (MCF-12A) cells and to correlate this effect with their effects 
      upon cellular characteristics associated with cancer progression (cell 
      proliferation, viability, migration, angiogenesis and apoptosis). (3)H-DG uptake 
      was markedly inhibited by a selective GLUT1 inhibitor (BAY-876) in all cell 
      lines, proving that (3)H-DG uptake is mainly GLUT1-mediated. TBH (2.5 muM), 
      insulin (50 nM), leptin (500 ng/ml) and INF-y (100 ng/ml) stimulate 
      GLUT1-mediated (3)H-DG (1 mM) uptake by both ER-positive and triple-negative 
      breast cancer cell lines. TBH and leptin, but not insulin and INF-gamma, increase 
      GLUT1 mRNA levels. Insulin and leptin (in both ER-positive and triple-negative 
      breast cancer cell lines) and TBH (in the triple-negative cell line) have a 
      proproliferative effect and leptin possesses a cytoprotective effect in both 
      breast cancer cell lines that can contribute to cancer progression. The effects 
      of TBH, insulin, leptin and INF-gamma upon breast cancer cell proliferation and 
      viability are GLUT1-dependent. In conclusion, T2DM-associated characteristics 
      induce changes in GLUT1-mediated glucose uptake that can contribute to cancer 
      progression. Moreover, we conclude that BAY-876 can be a strong candidate for 
      development of a new effective anticancer agent against breast cancer.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Silva, Claudia
AU  - Silva C
AD  - Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University 
      of Porto, Porto, Portugal; Instituto de Investigacao e Inovacao Em Saude (i3S), 
      University of Porto, Porto, Portugal.
FAU - Andrade, Nelson
AU  - Andrade N
AD  - Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University 
      of Porto, Porto, Portugal; Instituto de Investigacao e Inovacao Em Saude (i3S), 
      University of Porto, Porto, Portugal; REQUIMTE/LAQV, Department of Chemical 
      Sciences, Faculty of Pharmacy, University of Porto, Portugal.
FAU - Guimaraes, Joao Tiago
AU  - Guimaraes JT
AD  - Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University 
      of Porto, Porto, Portugal; Department of Clinical Pathology, Sao Joao Hospital 
      Centre, Porto, Portugal; Institute of Public Health, University of Porto, Porto, 
      Portugal.
FAU - Patricio, Emilia
AU  - Patricio E
AD  - Department of Clinical Pathology, Sao Joao Hospital Centre, Porto, Portugal.
FAU - Martel, Fatima
AU  - Martel F
AD  - Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University 
      of Porto, Porto, Portugal; Instituto de Investigacao e Inovacao Em Saude (i3S), 
      University of Porto, Porto, Portugal. Electronic address: fmartel@med.up.pt.
LA  - eng
PT  - Journal Article
DEP - 20210226
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antineoplastic Agents)
RN  - 0 (BAY-876)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
RN  - 0 (Pyrazoles)
RN  - 0 (Quinolines)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 955VYL842B (tert-Butylhydroperoxide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/drug therapy/*metabolism/pathology
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 1/antagonists & inhibitors/*metabolism
MH  - Humans
MH  - Insulin/*pharmacology
MH  - Interferon-gamma/*pharmacology
MH  - Leptin/*pharmacology
MH  - MCF-7 Cells
MH  - Neoplasm Invasiveness
MH  - Neovascularization, Pathologic
MH  - Oxidative Stress/*drug effects
MH  - Pyrazoles/pharmacology
MH  - Quinolines/pharmacology
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - tert-Butylhydroperoxide
OTO - NOTNLM
OT  - Breast cancer
OT  - Glucose transport
OT  - Insulin
OT  - Leptin
OT  - Oxidative stress
OT  - Type 2 diabetes mellitus
EDAT- 2021/03/02 06:00
MHDA- 2021/05/20 06:00
CRDT- 2021/03/01 20:11
PHST- 2020/12/10 00:00 [received]
PHST- 2021/02/15 00:00 [revised]
PHST- 2021/02/23 00:00 [accepted]
PHST- 2021/03/02 06:00 [pubmed]
PHST- 2021/05/20 06:00 [medline]
PHST- 2021/03/01 20:11 [entrez]
AID - S0014-2999(21)00133-3 [pii]
AID - 10.1016/j.ejphar.2021.173980 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2021 May 5;898:173980. doi: 10.1016/j.ejphar.2021.173980. Epub 
      2021 Feb 26.