دورية أكاديمية
Polymethoxylated flavones target cancer stemness and improve the antiproliferative effect of 5-fluorouracil in a 3D cell model of colorectal cancer
| العنوان: | Polymethoxylated flavones target cancer stemness and improve the antiproliferative effect of 5-fluorouracil in a 3D cell model of colorectal cancer |
|---|---|
| المؤلفون: | Pereira, Carolina V., Duarte, Marlene, Silva, Patrícia, Bento da Silva, Andreia, Duarte, Catarina M. M., Cifuentes, Alejandro, García-Cañas, Virginia, Bronze, Maria do Rosário, Albuquerque, Cristina, Serra, Ana Teresa |
| المساهمون: | Consejo Superior de Investigaciones Científicas (España), Ministério da Educação e Ciência (Portugal), European Commission, CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI), Fundação para a Ciência e a Tecnologia (Portugal) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute |
| سنة النشر: | 2019 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Orange peel extract, Polymethoxylated flavones, Tangeretin, Scutellarein tetramethylether, Synergistic interactions, 5-fluorouracil, Colorectal cancer, Cancer stem cells, 3D cell model |
| الوصف: | Polymethoxylated flavones (PMFs) from citrus fruits are reported to present anticancer potential. However, there is a lack of information regarding their effect on cancer stem cell (CSC) populations, which has been recognized as responsible for tumor initiation, relapse, and chemoresistance. In this study, we evaluated the effect of an orange peel extract (OPE) and its main PMFs, namely, nobiletin, sinensetin, tangeretin, and scutellarein tetramethylether in targeting cell proliferation and stemness using a 3D cell model of colorectal cancer composed of HT29 cell spheroids cultured for 7 days in stirred conditions. Soft agar assay, ALDH1 activity, and relative quantitative gene expression analysis of specific biomarkers were carried out to characterize the stemness, self-renewal, and mesenchymal features of HT29 cell spheroids. Then, the impact of OPE and PMFs in reducing cell proliferation and modulating cancer stemness and self-renewal was assessed. Results showed that, when compared with monolayer cultures, HT29 cell spheroids presented higher ALDH1 activity (81.97% ± 5.27% compared to 63.55% ± 17.49% for 2D), upregulation of CD44, PROM1, SOX9, and SNAI1 genes (1.83 ± 0.34, 2.54 ± 0.51, 2.03 ± 0.15, and 6.12 ± 1.59 times) and high self-renewal capability (352 ± 55 colonies compared to 253 ± 42 for 2D). Incubation with OPE (1 mg/mL) significantly inhibited cell proliferation and modulated cancer stemness and self-renewal ability: colony formation, ALDH1 activity, and the expression of cancer stemness biomarkers PROM1 and LGR5 were significantly reduced (0.66 ± 0.15 and 0.51 ± 0.14 times, respectively). Among all PMFs, tangeretin was the most efficient in targeting the CSC population by decreasing colony formation and the expression of PROM1 and LGR5. Scutellarein tetramethylether was shown to modulate markers of mesenchymal/metastatic transition (increasing CDH1 and reducing ZEB1 and SNAI1) and nobiletin was capable of downregulating PROM1 and SNAI1 expression. Importantly, all PMFs and OPE were shown to ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 2072-6643 |
| العلاقة: | Publisher's version; http://dx.doi.org/10.3390/nu11020326Test; Sí; Nutrients 11(2): 326 (2019); http://hdl.handle.net/10261/177053Test; http://dx.doi.org/10.13039/501100003381Test; http://dx.doi.org/10.13039/501100003339Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100001871Test |
| DOI: | 10.3390/nu11020326 |
| DOI: | 10.13039/501100003381 |
| DOI: | 10.13039/501100003339 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100001871 |
| الإتاحة: | https://doi.org/10.3390/nu11020326Test https://doi.org/10.13039/501100003381Test https://doi.org/10.13039/501100003339Test https://doi.org/10.13039/501100000780Test https://doi.org/10.13039/501100001871Test http://hdl.handle.net/10261/177053Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.D3AD2E2D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20726643 |
|---|---|
| DOI: | 10.3390/nu11020326 |