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- Title
Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells.
- Authors
Serambeque, Beatriz; Mestre, Catarina; Correia-Barros, Gabriela; Teixo, Ricardo; Marto, Carlos Miguel; Gonçalves, Ana Cristina; Caramelo, Francisco; Silva, Isabel; Paiva, Artur; Beck, Hans C.; Carvalho, Ana Sofia; Botelho, Maria Filomena; Carvalho, Maria João; Matthiesen, Rune; Laranjo, Mafalda
- Abstract
Simple Summary: Cancer stem cells (CSCs) are responsible for tumour initiation, growth, dissemination, and resistance to therapy. In this study, we intended to evaluate the effect of inhibiting aldehyde dehydrogenase (ALDH), an enzyme found in endometrial CSCs, using N,N-diethylaminobenzaldehyde (DEAB). Our findings suggest that ALDH blockage mediated by DEAB reduces enzyme activity and expression and can modulate CSC phenotype and behaviour. Additionally, DEAB modulates the expression of certain proteins, namely, ALDH18A1, SdhA, and UBAP2L, identified in endometrial cancer, which might be promising prognostic and therapeutic targets. ALDH inhibition could be a potential strategy to prevent endometrial CSCs from growing and spreading. 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.
- Subjects
RESEARCH funding; ALDEHYDE dehydrogenase; CELLULAR signal transduction; DESCRIPTIVE statistics; ENDOMETRIAL tumors; GENE expression; EXPERIMENTAL design; TUMOR suppressor genes; CELL lines; PROTEOMICS; WESTERN immunoblotting; MASS spectrometry; ONE-way analysis of variance; STEM cells; DISEASE progression; CHEMICAL inhibitors
- Publication
Cancers, 2024, Vol 16, Issue 11, p2031
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16112031