title: Role of ion channels in ionizing radiation-induced cell death.
abstract: Neoadjuvant, adjuvant or definitive fractionated radiation therapy are implemented in first line anti-cancer treatment regimens of many tumor entities. Ionizing radiation kills the tumor cells mainly by causing double strand breaks of their DNA through formation of intermediate radicals. Survival of the tumor cells depends on both, their capacity of oxidative defense and their efficacy of DNA repair. By damaging the targeted cells, ionizing radiation triggers a plethora of stress responses. Among those is the modulation of ion channels such as Ca2+-activated K+ channels or Ca2+-permeable nonselective cation channels belonging to the super-family of transient receptor potential channels. Radiogenic activation of these channels may contribute to radiogenic cell death as well as to DNA repair, glucose fueling, radiogenic hypermigration or lowering of the oxidative stress burden. The present review article introduces these channels and summarizes our current knowledge on the mechanisms underlying radiogenic ion channel modulation. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Germany. Electronic address: stephan.huber@uni-tuebingen.de.
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Germany; Department of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Butz
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stegen
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Klumpp
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Klumpp
authors.affiliation: Department of Radiation Oncology, University of Tübingen, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Eckert
mesh_terms: D016923:Cell Death / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020360:Neoadjuvant Therapy; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D018714:Radiotherapy, Adjuvant; D015398:Signal Transduction; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D024681:Potassium Channels, Calcium-Activated; D050051:Transient Receptor Potential Channels
keywords: Ca(2+)-activated K(+) channels; Cancer; Cell death; Ion transport; Radiation; Therapy resistance