Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells.

Autor: Serambeque B; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal., Mestre C; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal., Correia-Barros G; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal., Teixo R; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal., Marto CM; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Univ Coimbra, Institute of Experimental Pathology, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal., Gonçalves AC; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal.; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Laboratory of Oncobiology and Hematology (LOH) and University Clinics of Hematology and Oncology, Faculty of Medicine, 3000-548 Coimbra, Portugal., Caramelo F; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal.; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO) and Laboratory of Biostatistics and Medical Informatics (LBIM), Faculty of Medicine, 3004-531 Coimbra, Portugal., Silva I; Cytometry Operational Management Unit, Clinical Pathology Department, Unidade de Saúde Local de Coimbra, 3004-561 Coimbra, Portugal., Paiva A; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Cytometry Operational Management Unit, Clinical Pathology Department, Unidade de Saúde Local de Coimbra, 3004-561 Coimbra, Portugal.; Polytechnic Institute of Coimbra, Coimbra Health School, Laboratory Biomedical Sciences, 3045-043 Coimbra, Portugal., Beck HC; Department of Clinical Biochemistry, Odense University Hospital, 5000 Odense, Denmark., Carvalho AS; iNOVA4Health, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, 1150-082 Lisboa, Portugal., Botelho MF; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Univ Coimbra, Institute of Experimental Pathology, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal., Carvalho MJ; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal.; Univ Coimbra, Universitary Clinic of Gynecology, Faculty of Medicine, 3004-561 Coimbra, Portugal.; Gynecology Service, Department of Gynecology, Obstetrics, Reproduction and Neonatology, Unidade Local de Saúde de Coimbra, 3004-561 Coimbra, Portugal., Matthiesen R; iNOVA4Health, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, 1150-082 Lisboa, Portugal., Laranjo M; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), Institute of Biophysics, Faculty of Medicine, 3000-548 Coimbra, Portugal.; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 May 27; Vol. 16 (11). Date of Electronic Publication: 2024 May 27.
DOI: 10.3390/cancers16112031
Abstrakt: 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.
Databáze: MEDLINE
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