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Identification of natural products and FDA-approved drugs for targeting cancer stem cell (CSC) propagation

Bonuccelli, G; Sotgia, F; Lisanti, MP

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Authors

G Bonuccelli

F Sotgia

MP Lisanti



Abstract

Here, we report the identification of key compounds that effectively inhibit the anchorage-independent growth and propagation of cancer stem cells (CSCs), as determined via screening using MCF7 cells, a human breast adenocarcinoma cell line. More specifically, we employed the mammosphere assay as an experimental format, which involves the generation of 3D spheroid cultures, using low-attachment plates. These positive hit compounds can be divided into 5 categories: 1) dietary supplements (quercetin and glucosamine); 2) FDA-approved drugs (carvedilol and ciprofloxacin); 3) natural products (aloe emodin, aloin, tannic acid, chlorophyllin copper salt, azelaic acid and adipic acid); 4) flavours (citral and limonene); and 5) vitamins (nicotinamide and nicotinic acid). In addition, for the compounds quercetin, glucosamine and carvedilol, we further assessed their metabolic action, using the Seahorse to conduct metabolic flux analysis. Our results indicate that these treatments can affect glycolytic flux and suppress oxidative mitochondrial metabolism (OXPHOS). Therefore, quercetin, glucosamine and carvedilol can reprogram the metabolic phenotype of breast cancer cells. Despite having diverse chemical structures, these compounds all interfere with mitochondrial metabolism. As these compounds halt CSCs propagation, ultimately, they may have therapeutic potential.

Citation

Bonuccelli, G., Sotgia, F., & Lisanti, M. (2022). Identification of natural products and FDA-approved drugs for targeting cancer stem cell (CSC) propagation. Aging, 14(23), 9466-9483. https://doi.org/10.18632/aging.204412

Journal Article Type Article
Acceptance Date Nov 17, 2022
Publication Date Dec 1, 2022
Deposit Date Jan 12, 2023
Publicly Available Date Jan 12, 2023
Journal Aging
Publisher Impact Journals
Volume 14
Issue 23
Pages 9466-9483
DOI https://doi.org/10.18632/aging.204412
Publisher URL https://doi.org/10.18632/aging.204412

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