Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide
Cámara-Sánchez, Patricia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Díaz Riascos, Zamira Vanessa (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García Aranda, Natalia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gener, Petra (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Seras-Franzoso, Joaquin (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Giani-Alonso, Micaela (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Royo, Miriam (Institut de Química Avançada de Catalunya)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Schwartz, Simon (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Abasolo, Ibane (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí"

Data:	2022
Resum:	Cancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments.
Ajuts:	Fundació la Marató de TV3 337/C/2013 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-638 European Commission 800983
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Triple negative breast cancer ; Cancer stem cells ; 8-quinolinol ; Niclosamide ; Combination therapy
Publicat a:	International journal of molecular sciences, Vol. 23, Issue 19 (October 2022) , art. 11760, ISSN 1422-0067

DOI: 10.3390/ijms231911760
PMID: 36233074

25 p, 4.8 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Biotecnologia i de Biomedicina (IBB)
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