Autophagy induction by thiostrepton for the improvement of anticancer therapy. Issue 6 (2nd June 2020)

• Record Type: Journal Article
• Authors: Kepp, Oliver; Kroemer, Guido
• Is Part Of: Autophagy. Volume 16:Issue 6(2020)
• Page Start: 1166
• Page End: 1167
• Publication Date: 2020-06-02
• Subjects: Anticancer immunity -- caloric restriction mimetic -- danger associated molecular pattern -- high-content screening -- immunogenic cell death; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2020.1758417
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: Macroautophagy/autophagy induction by caloric restriction mimetics (CRMs) is a strategy to stimulate anticancer immune responses of immunogenic cell death (ICD)-inducing chemotherapeutics. We designed a phenotypic screening campaign in which we identified pharmacological agents that have CRM properties (i.e., non-cytotoxic induction of autophagic flux that reduces cytoplasmic protein acetylation) and simultaneously act as ICD amplifiers (i.e. with the capacity to enhance the release of adenosine triphosphate, ATP, from stressed and dying cancer cells). This approach led to the identification of thiostrepton, a natural cyclic oligopeptide antibiotic, as an agent that enhances chemotherapy-induced anticancer immune responses in vivo, in immunocompetent mice bearing syngeneic tumors. Interestingly, both the pro-autophagic and the anticancer effects of thiostrepton rely on the activation of TFEB (transcription factor EB) and TFE3 (transcription factor E3). In summary, thiostrepton represents a novel CRM and ICD amplifier that may be useful for cancer therapy.