Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer

Regulated cell death by way of ferroptosis involves iron-dependent accumulation of cellular reactive oxygen species (ROS). Ferroptosis is attracting attention as a potential therapeutic target for cancer treatments without drug resistance. The relationship between irisin, a myokine involved in autop...

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Main Authors: Bao Chen Yang, Po Sing Leung
Format: Article
Language:English
Published: Elsevier 2020-09-01
Series:Molecular Therapy: Oncolytics
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2372770520301194
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author Bao Chen Yang
Po Sing Leung
author_facet Bao Chen Yang
Po Sing Leung
author_sort Bao Chen Yang
collection DOAJ
description Regulated cell death by way of ferroptosis involves iron-dependent accumulation of cellular reactive oxygen species (ROS). Ferroptosis is attracting attention as a potential therapeutic target for cancer treatments without drug resistance. The relationship between irisin, a myokine involved in autophagy and ROS metabolism, and ferroptosis is unclear. In this study, we used erastin-induced ferroptosis in PANC-1 cells to examine potential interactions of irisin with ferroptosis. Using western blots and reverse transcriptase polymerase chain reactions, we found that irisin can further exacerbate erastin-induced upregulation in free iron, lipid ROS levels, and glutathione depletion, relative to cells treated with erastin only. Conversely, removal of irisin limited erastin effects. Furthermore, irisin modulation of ferroptosis was associated with the expression changes in molecules important for ROS metabolism, iron metabolism, and the cysteine/glutamate antiporter system (system Xc−). These study findings suggest that irisin can act as a master factor of ferroptosis, and that potential implications for harnessing irisin-mediated ferroptosis for cancer treatment are warranted.
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spelling doaj.art-1e6e8746fb4040c794184f766f1c20342022-12-22T00:55:49ZengElsevierMolecular Therapy: Oncolytics2372-77052020-09-0118457466Irisin Is a Positive Regulator for Ferroptosis in Pancreatic CancerBao Chen Yang0Po Sing Leung1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Corresponding author: Po Sing Leung, PhD, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Room 609A, 6/F, Lo Kwee-Seong Integrated Biomedical Sciences Building, Hong Kong, China.Regulated cell death by way of ferroptosis involves iron-dependent accumulation of cellular reactive oxygen species (ROS). Ferroptosis is attracting attention as a potential therapeutic target for cancer treatments without drug resistance. The relationship between irisin, a myokine involved in autophagy and ROS metabolism, and ferroptosis is unclear. In this study, we used erastin-induced ferroptosis in PANC-1 cells to examine potential interactions of irisin with ferroptosis. Using western blots and reverse transcriptase polymerase chain reactions, we found that irisin can further exacerbate erastin-induced upregulation in free iron, lipid ROS levels, and glutathione depletion, relative to cells treated with erastin only. Conversely, removal of irisin limited erastin effects. Furthermore, irisin modulation of ferroptosis was associated with the expression changes in molecules important for ROS metabolism, iron metabolism, and the cysteine/glutamate antiporter system (system Xc−). These study findings suggest that irisin can act as a master factor of ferroptosis, and that potential implications for harnessing irisin-mediated ferroptosis for cancer treatment are warranted.http://www.sciencedirect.com/science/article/pii/S2372770520301194autophagyerastinferroptosisirisinPANC-1 cellsROS
spellingShingle Bao Chen Yang
Po Sing Leung
Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer
Molecular Therapy: Oncolytics
autophagy
erastin
ferroptosis
irisin
PANC-1 cells
ROS
title Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer
title_full Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer
title_fullStr Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer
title_full_unstemmed Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer
title_short Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer
title_sort irisin is a positive regulator for ferroptosis in pancreatic cancer
topic autophagy
erastin
ferroptosis
irisin
PANC-1 cells
ROS
url http://www.sciencedirect.com/science/article/pii/S2372770520301194
work_keys_str_mv AT baochenyang irisinisapositiveregulatorforferroptosisinpancreaticcancer
AT posingleung irisinisapositiveregulatorforferroptosisinpancreaticcancer