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Transferrin-based radiolabeled probe predicts the sensitivity of human renal cancer cell lines to ferroptosis inducer erastin

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Title: Transferrin-based radiolabeled probe predicts the sensitivity of human renal cancer cell lines to ferroptosis inducer erastin
Authors: Shibata, Yuki Browse this author
Yasui, Hironobu Browse this author →KAKEN DB
Higashikawa, Kei Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Keywords: Ferroptosis
Transferrin Receptor-1
Renal cancer
Issue Date: Jul-2021
Publisher: Elsevier
Journal Title: Biochemistry and Biophysics Reports
Volume: 26
Start Page: 100957
Publisher DOI: 10.1016/j.bbrep.2021.100957
Abstract: Ferroptosis induction has been recognized as a novel cancer therapeutic strategy. To effectively apply ferroptosis-targeting cancer therapy to individual patients, a diagnostic indicator for selecting this therapeutic strategy from a number of molecular targeting drugs is needed. However, to date, methods that can predict the efficacy of ferroptosis-targeting treatment have not been established yet. In this study, we focused on the iron metabolic pathway to develop a nuclear imaging technique for diagnosing the susceptibility of cancer cells to ferroptosis. As a nuclear probe, human transferrin (Tf) was labeled with Gallium-68 (Ga-68) using 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as a chelator (Ga-68-NOTA-Tf). Western blot assay and clonogenic survival assay with human renal cancer cell lines A498 and 786-O revealed that the protein expression level of transferrin receptor1 (TfR1) and sensitivity to a ferroptosis inducer, erastin, were correlated. A cellular uptake assay with Ga-68-NOTA-Tf revealed that the cancer cells sensitive to erastin highly internalized the Ga-68-NOTA-Tf. Furthermore, treatment with the TfR1 inhibitor ferristatin II reduced the cellular uptake of Ga-68-NOTA-Tf, indicating that the intracellular uptake of the probe was mediated by TfR1. These results suggest that Ga-68-NOTA-Tf can be useful in predicting the sensitivity of cancer cells to ferroptosis inducers.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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