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Interplay between Cellular Uptake, Intracellular Localization and the Cell Death Mechanism in Triphenylamine-Mediated Photoinduced Cell Death

Authors
  • Chennoufi, Rahima1
  • Trinh, Ngoc-Duong1
  • Simon, Françoise1
  • Bordeau, Guillaume2, 3
  • Naud-Martin, Delphine2
  • Moussaron, Albert4
  • Cinquin, Bertrand1
  • Bougherara, Houcine5, 6
  • Rambaud, Béatrice1
  • Tauc, Patrick1
  • Frochot, Céline4
  • Teulade-Fichou, Marie-Paule2
  • Mahuteau-Betzer, Florence2
  • Deprez, Eric1
  • 1 Laboratory of Biology and Applied Pharmacology (LBPA), CNRS UMR8113, IDA FR3242, ENS Paris-Saclay, Université Paris-Saclay, Gif-sur-Yvette, F-91190, France , Gif-sur-Yvette (France)
  • 2 UMR9187, CNRS, INSERM, Institut Curie, PSL Research University, Université Paris-Saclay, Orsay, F-91405, France , Orsay (France)
  • 3 Laboratoire des IMRCP, Université de Toulouse, CNRS UMR5623, Université Toulouse-III - Paul Sabatier, Toulouse, F-31400, France , Toulouse (France)
  • 4 LRGP, UMR7274 CNRS-Université de Lorraine, Nancy, F-54000, France , Nancy (France)
  • 5 Institut Cochin, INSERM U1016-CNRS UMR8104-Université Paris Descartes, Sorbonne Paris Cité, Paris, F-75014, France , Paris (France)
  • 6 Institut de Recherches Servier SA, Croissy-sur-Seine, F-78290, France , Croissy-sur-Seine (France)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Apr 23, 2020
Volume
10
Issue
1
Identifiers
DOI: 10.1038/s41598-020-63991-9
Source
Springer Nature
License
Green

Abstract

Triphenylamines (TPAs) were previously shown to trigger cell death under prolonged one- or two-photon illumination. Their initial subcellular localization, before prolonged illumination, is exclusively cytoplasmic and they translocate to the nucleus upon photoactivation. However, depending on their structure, they display significant differences in terms of precise initial localization and subsequent photoinduced cell death mechanism. Here, we investigated the structural features of TPAs that influence cell death by studying a series of molecules differing by the number and chemical nature of vinyl branches. All compounds triggered cell death upon one-photon excitation, however to different extents, the nature of the electron acceptor group being determinant for the overall cell death efficiency. Photobleaching susceptibility was also an important parameter for discriminating efficient/inefficient compounds in two-photon experiments. Furthermore, the number of branches, but not their chemical nature, was crucial for determining the cellular uptake mechanism of TPAs and their intracellular fate. The uptake of all TPAs is an active endocytic process but two- and three-branch compounds are taken up via distinct endocytosis pathways, clathrin-dependent or -independent (predominantly caveolae-dependent), respectively. Two-branch TPAs preferentially target mitochondria and photoinduce both apoptosis and a proper necrotic process, whereas three-branch TPAs preferentially target late endosomes and photoinduce apoptosis only.

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