MitoTam induces ferroptosis and increases radiosensitivity in head and neck cancer cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00598553" target="_blank" >RIV/86652036:_____/24:00598553 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/24:10497658 RIV/00216208:11310/24:10497658

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0167814024007734?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0167814024007734?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.radonc.2024.110503" target="_blank" >10.1016/j.radonc.2024.110503</a>

Result language

angličtina

Original language name

MitoTam induces ferroptosis and increases radiosensitivity in head and neck cancer cells

Original language description

Background and purpose: Radiotherapy (RT) is an integral treatment part for patients with head and neck squamous cell carcinoma (HNSCC), but radioresistance remains a major issue. Here, we use MitoTam, a mitochondrially targeted analogue of tamoxifen, which we aim to stimulate ferroptotic cell death with, and sensitize radioresistant cells to RT. Materials and methods: We assessed viability, reactive oxygen species (ROS) production, disruption of mitochondrial membrane potential, and lipid peroxidation in radiosensitive (UT-SCC-40) and radioresistant (UT-SCC5) HNSCC cells following MitoTam treatment. To assess ferroptosis specificity, we used the ferroptosis inhibitor ferrostatin-1 (fer-1). Also, total antioxidant capacity and sensitivity to tert-butyl hydroperoxide were evaluated to assess ROS-responses. 53BP1 staining was used to assess radiosensitivity after MitoTam treatment. Results: Our data revealed increased ROS, cell death, disruption of mitochondrial membrane potential, and lipid peroxidation following MitoTam treatment in both cell lines. Adverse effects of MitoTam on cell death, membrane potential and lipid peroxidation were prevented by fer-1, indicating induction of ferroptosis. Radioresistant HNSCC cells were less sensitive to the effects of MitoTam due to intrinsic higher antioxidant capacity. MitoTam treatment prior to RT led to superadditive residual DNA damage expressed by 53BP1 foci compared to RT or MitoTam alone. Conclusion: MitoTam induced ferroptosis in HNSCC cells, which could be used to overcome the elevated antioxidant capacity of radioresistant cells and sensitize such cells to RT. Treatment with MitoTam followed by RT could therefore present a promising effective therapy of radioresistant cancers. Statement of significance. Radiotherapy is applied in the treatment of a majority of cancer patients. Radioresistance due to elevated antioxidant levels can be overcome by promoting ferroptotic cell death combining ROS-inducing drug MitoTam with radiotherapy.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30224 - Radiology, nuclear medicine and medical imaging

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Radiotherapy and Oncology

ISSN

0167-8140

e-ISSN

1879-0887

Volume of the periodical

200

Issue of the periodical within the volume

NOV 2024

Country of publishing house

IE - IRELAND

Number of pages

7

Pages from-to

110503

UT code for WoS article

001309762800001

EID of the result in the Scopus database

2-s2.0-85202507103