Calcium, oxidative stress and connexin channels, a harmonious orchestra directing the response to radiotherapy treatment?

Research output: Contribution to journalLiterature review


Institutes & Expert groups

  • UGent - Universiteit Gent
  • KUL - Katholieke Universiteit Leuven
  • VUB - Vrije Universiteit Brussel

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Although radiotherapy is commonly used to treat cancer, its beneficial outcome is frequently hampered by the radiation resistance of tumor cells and adverse reactions in normal tissues. Mechanisms of cell-to-cell communication and how intercellular signals are translated into cellular responses, have become topics of intense investigation, particularly within the field of radiobiology. A substantial amount of evidence is available demonstrating that both gap junctional and paracrine communication pathways can propagate radiation-induced biological effects at the intercellular level, commonly referred to as radiation-induced bystander effects (RIBE). Multiple molecular signaling mechanisms involving oxidative stress, kinases, inflammatory molecules, and Ca2+ are postulated to contribute to RIBE. Ca2+ is a highly versatile and ubiquitous second messenger that regulates diverse cellular processes via the interaction with various signaling cascades. It furthermore provides a fast system for the dissemination of information at the intercellular level. Channels formed by transmembrane connexin (Cx) proteins, i.e. hemichannels and gap junction channels, can mediate the cell-to-cell propagation of increases in intracellular Ca2+ by ministering paracrine and direct cell-cell communication, respectively. We here review current knowledge on radiation-induced signaling mechanisms in irradiated and bystander cells, particularly focusing on the contribution of oxidative stress, Ca2+ and Cx channels. By illustrating the tight interplay between these different partners, we provide a conceptual framework for intercellular Ca2+ signaling as a key player in modulating the RIBE and the overall response to radiation. Copyright � 2017 Elsevier B.V. All rights reserved.


Original languageEnglish
Pages (from-to)1099-1120
Number of pages21
JournalBiochimica et Biophysica Acta
Issue number6
Publication statusPublished - 1 Jun 2017


  • Ionizing radioation, Calcium, Oxidative stress, Connexin hemichannel, gap junction, Bystander effect

ID: 3029444