Brecht 2016 Toxicol In Vitro

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Brecht K, Riebel V, Couttet P, Paech F, Wolf A, Chibout SD, Pognan F, Krähenbühl S, Uteng M (2016) Mechanistic insights into selective killing of OXPHOS-dependent cancer cells by arctigenin. Toxicol In Vitro 40:55-65.

» PMID: 27923774 Open Access

Brecht K, Riebel V, Couttet P, Paech F, Wolf A, Chibout SD, Pognan F, Kraehenbuehl S, Uteng M (2016) Toxicol In Vitro

Abstract: Arctigenin has previously been identified as a potential anti-tumor treatment for advanced pancreatic cancer. However, the mechanism of how arctigenin kills cancer cells is not fully understood. In the present work we studied the mechanism of toxicity by arctigenin in the human pancreatic cell line, Panc-1, with special emphasis on the mitochondria. A comparison of Panc-1 cells cultured in glucose versus galactose medium was applied, allowing assessments of effects in glycolytic versus oxidative phosphorylation (OXPHOS)-dependent Panc-1 cells. For control purposes, the mitochondrial toxic response to treatment with arctigenin was compared to the anti-cancer drug, sorafenib, which is a tyrosine kinase inhibitor known for mitochondrial toxic off-target effects (Will et al., 2008). In both Panc-1 OXPHOS-dependent and glycolytic cells, arctigenin dissipated the mitochondrial membrane potential, which was demonstrated to be due to inhibition of the mitochondrial complexes II and IV. However, arctigenin selectively killed only the OXPHOS-dependent Panc-1 cells. This selective killing of OXPHOS-dependent Panc-1 cells was accompanied by generation of ER stress, mitochondrial membrane permeabilization and caspase activation leading to apoptosis and aponecrosis.

Copyright © 2016 Elsevier Ltd. All rights reserved.

Keywords: Arctigenin, Mitochondrial toxicity, Panc-1 human pancreatic epithelioid carcinoma cells, Pancreatic cancer, Sorafenib

O2k-Network Lab: CH Basel Kraehenbuehl S, CH Basel Uteng M


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer 

Organism: Human  Tissue;cell: Islet cell;pancreas;thymus  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, DQ, CIV, Other combinations, ROX  HRR: Oxygraph-2k