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Thioalbamide, A Thioamidated Peptide from Amycolatopsis alba, Affects Tumor Growth and Stemness by Inducing Metabolic Dysfunction and Oxidative Stress

1
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende (CS), Italy
2
Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester M5 4WT, UK
3
Department of Molecular Microbiology, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally and should be considered co-first authors.
Cells 2019, 8(11), 1408; https://doi.org/10.3390/cells8111408
Received: 4 September 2019 / Revised: 4 November 2019 / Accepted: 7 November 2019 / Published: 8 November 2019
Thioalbamide, a thioamidated peptide biosynthesized by Amycolatopsis alba, is a thioviridamide-like molecule, and is part of a family of natural products representing a focus of biotechnological and pharmaceutical research in recent years due to their potent anti-proliferative and cytotoxic activities on malignant cells. Despite the high antitumor potential observed at nanomolar concentrations, the mechanisms underlying thioalbamide activity are still not known. In this work, the cellular effects induced by thioalbamide treatment on breast cancer cell lines were evaluated for the first time, highlighting the ability of this microbial natural peptide to induce mitochondrial dysfunction, oxidative stress, and apoptotic cell death. Furthermore, we demonstrate that thioalbamide can inhibit the propagation of cancer stem-like cells, which are strongly dependent on mitochondrial function and are responsible for chemotherapy resistance, metastasis, and tumor recurrence. View Full-Text
Keywords: thioviridamide-like molecules; RiPPs; natural products; anticancer agent; cancer stem cells thioviridamide-like molecules; RiPPs; natural products; anticancer agent; cancer stem cells
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Frattaruolo, L.; Fiorillo, M.; Brindisi, M.; Curcio, R.; Dolce, V.; Lacret, R.; Truman, A.W.; Sotgia, F.; Lisanti, M.P.; Cappello, A.R. Thioalbamide, A Thioamidated Peptide from Amycolatopsis alba, Affects Tumor Growth and Stemness by Inducing Metabolic Dysfunction and Oxidative Stress. Cells 2019, 8, 1408.

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