TY - JOUR
T1 - Autophagy induction by thiostrepton for the improvement of anticancer therapy
AU - Kepp, Oliver
AU - Kroemer, Guido
N1 - Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/6/2
Y1 - 2020/6/2
N2 - 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.
AB - 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.
KW - Anticancer immunity
KW - caloric restriction mimetic
KW - danger associated molecular pattern
KW - high-content screening
KW - immunogenic cell death
UR - http://www.scopus.com/inward/record.url?scp=85084258864&partnerID=8YFLogxK
U2 - 10.1080/15548627.2020.1758417
DO - 10.1080/15548627.2020.1758417
M3 - Article
C2 - 32330398
AN - SCOPUS:85084258864
SN - 1554-8627
VL - 16
SP - 1166
EP - 1167
JO - Autophagy
JF - Autophagy
IS - 6
ER -