Article, 2024
Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells
Cancers,
ISSN
2072-6694,
Volume 16,
11,
Page 2031,
10.3390/cancers16112031
Contributors
Serambeque, Beatriz Prazeres
0000-0002-3634-859X
(Corresponding author)
[1]
Mestre, Catarina
[1]
Correia-Barros, Gabriela
[1]
Teixo, Ricardo Jorge Marques
0000-0002-1317-3352
[1]
Marto, Carlos Miguel Machado
0000-0001-9269-5417
[1]
[2]
Gonçalves, Ana Cristina
0000-0003-1470-4802
[1]
[2]
Caramelo, Francisco José Santiago Fernandes Amado
0000-0002-0015-8604
[1]
[2]
Silva, Isabel Maria Melo
[3]
Paiva, Artur Augusto
0000-0002-6562-5859
[1]
[3]
[4]
Beck, Hans Christian
0000-0002-7763-3637
[5]
Carvalho, Ana Sofia Leitão
0000-0003-0657-1907
[6]
[7]
Botelho, Maria Filomena Rabaça Roque
0000-0001-7202-1650
[1]
[2]
Carvalho, Maria João
0000-0001-9409-5466
[1]
[2]
[8]
Matthiesen, Rune
0000-0002-6353-2616
[6]
[7]
Laranjo, Mafalda
0000-0003-0689-6007
(Corresponding author)
[1]
[2]
Affiliations
- [1]
University of Coimbra
[NORA names:
Portugal; Europe, EU; OECD];
- [2]
Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal
[NORA names:
Portugal; Europe, EU; OECD];
- [3]
Cytometry Operational Management Unit, Clinical Pathology Department, Unidade de Saúde Local de Coimbra, 3004-561 Coimbra, Portugal;, 14546@ulscoimbra.min-saude.pt
[NORA names:
Portugal; Europe, EU; OECD];
- [4]
Polytechnic Institute of Coimbra
[NORA names:
Portugal; Europe, EU; OECD];
- [5]
Odense University Hospital
[NORA names:
Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
(... more)
- [6]
NOVA4Health, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, 1150-082 Lisboa, Portugal;, ana.carvalho@nms.unl.pt, (A.S.C.);, rune.matthiesen@nms.unl.pt, (R.M.)
- [7]
Universidade Nova de Lisboa
[NORA names:
Portugal; Europe, EU; OECD];
- [8]
Gynecology Service, Department of Gynecology, Obstetrics, Reproduction and Neonatology, Unidade Local de Saúde de Coimbra, 3004-561 Coimbra, Portugal
[NORA names:
Portugal; Europe, EU; OECD]
(less)
Abstract
Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.
Keywords
ALDH activity,
ALDH inhibition,
ALDH18A1,
CD133,
CD133 expression,
CD24,
CD44,
CSC phenotype,
DEAB,
ECC-1,
N,N-diethylaminobenzaldehyde,
RL95,
RL95-2 cells,
SDHA,
UBAP2L,
activity,
aldehyde dehydrogenase,
aldehyde dehydrogenase activity,
aldehyde dehydrogenase inhibition,
aldehydes,
area,
associated with invasion,
cancer,
cancer cells,
cancer stem cells,
capacity,
cells,
chemotherapy,
chemotherapy resistance,
decrease,
dehydrogenase,
disease,
disease progression,
down-regulated proteins,
early stages,
effect,
endometrial cancer,
endometrial cancer cells,
endometrial cancer stem cells,
expression,
gynaecological malignancies,
increased CD133 expression,
influence,
inhibition,
invasion,
malignancy,
mass spectrometry-based proteomic studies,
metastasis,
metastatic disease,
molecular targets,
p53,
p53 expression,
patients,
phenotype,
profile,
progression,
project,
project area,
protein,
proteomic profiling,
proteomic studies,
protocol,
recurrence,
resistance,
self-renewal,
sphere-forming capacity,
stage,
stem,
stem cells,
study,
target,
treatment,
trigger tumorigenesis,
tumorigenesis,
up-regulated
Funders
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