Single and double modified salinomycin analogs target stem-like cells in 2D and 3D breast cancer models
| Autor: | Timothy C. Chambers, Adam Huczyński, Angus M. MacNicol, Alicja Urbaniak, Anika Moorjani, Melanie C. MacNicol, Robert L. Eoff, Daniel Fil, Michał Sulik, Michalina Kupsik, Michał Antoszczak, Megan R. Reed, Sarah Heflin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Organoid
0301 basic medicine Cell Breast Neoplasms RM1-950 Article Metastasis 03 medical and health sciences chemistry.chemical_compound Breast cancer 0302 clinical medicine Cancer stem cell Cell Movement Cell Line Tumor Drug Discovery medicine Humans Salinomycin Pyrans Pharmacology Stem cell Antibiotics Antineoplastic biology business.industry CD44 CD24 Antigen General Medicine medicine.disease 030104 developmental biology medicine.anatomical_structure Hyaluronan Receptors chemistry Cell culture 030220 oncology & carcinogenesis biology.protein Cancer research MCF-7 Cells Neoplastic Stem Cells Female Therapeutics. Pharmacology Drug Screening Assays Antitumor business Cell Division |
| Zdroj: | Biomed Pharmacother Biomedicine & Pharmacotherapy, Vol 141, Iss, Pp 111815-(2021) |
| Popis: | Breast cancer remains one of the leading cancers among women. Cancer stem cells (CSCs) are tumor-initiating cells which drive progression, metastasis, and reoccurrence of the disease. CSCs are resistant to conventional chemo- and radio-therapies and their ability to survive such treatment enables tumor reestablishment. Metastasis is the main cause of mortality in women with breast cancer, thus advances in treatment will depend on therapeutic strategies targeting CSCs. Salinomycin (SAL) is a naturally occurring polyether ionophore antibiotic known for its anticancer activity towards several types of tumor cells. In the present work, a library of 17 C1-single and C1/C20-double modified SAL analogs was screened to identify compounds with improved activity against breast CSCs. Six single- and two double-modified analogs were more potent (IC50 range of 1.1 ± 0.1–1.4 ± 0.2 µM) toward the breast cancer cell line MDA-MB-231 compared to SAL (IC50 of 4.9 ± 1.6 µM). Double-modified compound 17 was found to be more efficacious than SAL against the majority of cancer cell lines in the NCI-60 Human Tumor Cell Line Panel. Compound 17 was more potent than SAL in inhibiting cell migration and cell renewal properties of MDA-MB-231 cells, as well as inducing selective loss of the CD44+/CD24 /low stem-cell-like subpopulation in both monolayer (2D) and organoid (3D) culture. The present findings highlight the therapeutic potential of SAL analogs towards breast CSCs and identify select compounds that merit further study and clinical development. |
| Databáze: | OpenAIRE |
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