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APD-Containing Cyclolipodepsipeptides Target Mitochondrial Function in Hypoxic Cancer Cells.
Jacobsen, Kristian Mark; Villadsen, Nikolaj Lilholm; Tørring, Thomas; Nielsen, Camilla Bak; Salomón, Trine; Nielsen, Morten Muhlig; Tsakos, Michail; Sibbersen, Christian; Scavenius, Carsten; Nielsen, Rikke; Christensen, Erik Ilsø; Guerra, Paula Fernandez; Bross, Peter; Pedersen, Jakob Skou; Enghild, Jan Johannes; Johannsen, Mogens; Frøkiær, Jørgen; Overgaard, Jens; Horsman, Michael R; Busk, Morten; Poulsen, Thomas B.
Affiliation
  • Jacobsen KM; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
  • Villadsen NL; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
  • Tørring T; Department of Engineering, Aarhus University, 8000 Aarhus C, Denmark.
  • Nielsen CB; Department of Forensic Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Salomón T; Department of Forensic Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Nielsen MM; Department of Molecular Medicine (MOMA), Aarhus University Hospital, 8200 Aarhus N, Denmark.
  • Tsakos M; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
  • Sibbersen C; Department of Forensic Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Scavenius C; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark.
  • Nielsen R; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
  • Christensen EI; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
  • Guerra PF; Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark.
  • Bross P; Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark.
  • Pedersen JS; Department of Molecular Medicine (MOMA), Aarhus University Hospital, 8200 Aarhus N, Denmark; Bioinformatics Research Center, BiRC, Aarhus University, 8000 Aarhus C, Denmark.
  • Enghild JJ; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark; Interdisciplinary Nanoscience Center, iNANO, Aarhus University, 8000 Aarhus C, Denmark.
  • Johannsen M; Department of Forensic Medicine, Aarhus University, 8200 Aarhus N, Denmark.
  • Frøkiær J; Department of Nuclear Medicine and PET Center, Aarhus University Hospital, 8200 Aarhus N, Denmark.
  • Overgaard J; Department of Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus C, Denmark.
  • Horsman MR; Department of Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus C, Denmark.
  • Busk M; Department of Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus C, Denmark.
  • Poulsen TB; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark. Electronic address: thpou@chem.au.dk.
Cell Chem Biol ; 25(11): 1337-1349.e12, 2018 11 15.
Article in En | MEDLINE | ID: mdl-30122371
The natural product family of macrocyclic lipodepsipeptides containing the 4-amido-2,4-pentadienoate functionality possesses intriguing cytotoxic selectivity toward hypoxic cancer cells. These subpopulations of cancer cells display increased metastatic potential and resistance to chemo- and radiotherapy. In this paper, we present studies on the mechanism of action of these natural products in hypoxic cancer cells and show that this involves rapid and hypoxia-selective collapse of mitochondrial integrity and function. These events drive a regulated cell death process that potentially could function as a powerful tool in the fight against chemo- and radiotherapy-resistant cancer cells. Toward that end, we demonstrate activity in two different mouse tumor models.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Depsipeptides / Tumor Hypoxia / Mitochondria / Antineoplastic Agents Limits: Animals / Female / Humans / Male Language: En Journal: Cell Chem Biol Year: 2018 Document type: Article Affiliation country: Denmark Country of publication: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Depsipeptides / Tumor Hypoxia / Mitochondria / Antineoplastic Agents Limits: Animals / Female / Humans / Male Language: En Journal: Cell Chem Biol Year: 2018 Document type: Article Affiliation country: Denmark Country of publication: United States