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Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue
Published on: May 17, 2018
APD-Containing Cyclolipodepsipeptides Target Mitochondrial Function in Hypoxic Cancer Cells
Kristian Mark Jacobsen1, Nikolaj Lilholm Villadsen1, Thomas Tørring2
1Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
Abstract:
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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