Thioalbamide, a thioamidated peptide from Amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress

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.