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Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis

PURPOSE: The anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignan...

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Autores principales: Zhu, Zeen, Wang, Xueni, Zhang, Wunai, Gong, Mengyuan, Zhang, Simei, Yang, Bao, Qu, Bolun, Wu, Zheng, Ma, Qingyong, Wang, Zheng, Qian, Weikun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561879/
https://www.ncbi.nlm.nih.gov/pubmed/36248959
http://dx.doi.org/10.3389/fonc.2022.960858
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author Zhu, Zeen
Wang, Xueni
Zhang, Wunai
Gong, Mengyuan
Zhang, Simei
Yang, Bao
Qu, Bolun
Wu, Zheng
Ma, Qingyong
Wang, Zheng
Qian, Weikun
author_facet Zhu, Zeen
Wang, Xueni
Zhang, Wunai
Gong, Mengyuan
Zhang, Simei
Yang, Bao
Qu, Bolun
Wu, Zheng
Ma, Qingyong
Wang, Zheng
Qian, Weikun
author_sort Zhu, Zeen
collection PubMed
description PURPOSE: The anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignant tumours. We aimed to explore the potential therapeutic role of Huaier in pancreatic cancer and uncover the relationship between Huaier and ferroptosis. METHODS: CCK8 and colony formation assays were used to determine the proliferation of pancreatic cancer cells (PCs). The levels of cellular ROS were analysed by a fluorescence probe, and the accumulation of cellular iron was showed by Prussian blue staining. The autophagosomes and mitochondrial morphology were characterised by transmission electron microscopy (TEM). The levels of intracellular glutathione (GSH) and lipid peroxidation were measured by the corresponding kits. RESULTS: The growth inhibitory effect of Huaier on PCs was concentration- and time-dependent, but this effect was significantly attenuated by ferroptosis inhibitors. In addition, Huaier effectively inhibited the GSH–GPX4 antioxidation system and resulted in the massive accumulation of ROS in PCs As shown by TEM, Huaier-treated PCs exhibited a decrease in mitochondrial cristae and a smaller mitochondrion, accompanied by an increase in autophagosomes. Indeed, we found that autophagy can induce ferroptosis in PCs and that Huaier-induced ferroptosis can be suppressed by the autophagosome inhibitor, Wortmannin. CONCLUSION: Huaier can activate ferroptosis by inducing autophagy in PCs.
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spelling pubmed-95618792022-10-15 Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis Zhu, Zeen Wang, Xueni Zhang, Wunai Gong, Mengyuan Zhang, Simei Yang, Bao Qu, Bolun Wu, Zheng Ma, Qingyong Wang, Zheng Qian, Weikun Front Oncol Oncology PURPOSE: The anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignant tumours. We aimed to explore the potential therapeutic role of Huaier in pancreatic cancer and uncover the relationship between Huaier and ferroptosis. METHODS: CCK8 and colony formation assays were used to determine the proliferation of pancreatic cancer cells (PCs). The levels of cellular ROS were analysed by a fluorescence probe, and the accumulation of cellular iron was showed by Prussian blue staining. The autophagosomes and mitochondrial morphology were characterised by transmission electron microscopy (TEM). The levels of intracellular glutathione (GSH) and lipid peroxidation were measured by the corresponding kits. RESULTS: The growth inhibitory effect of Huaier on PCs was concentration- and time-dependent, but this effect was significantly attenuated by ferroptosis inhibitors. In addition, Huaier effectively inhibited the GSH–GPX4 antioxidation system and resulted in the massive accumulation of ROS in PCs As shown by TEM, Huaier-treated PCs exhibited a decrease in mitochondrial cristae and a smaller mitochondrion, accompanied by an increase in autophagosomes. Indeed, we found that autophagy can induce ferroptosis in PCs and that Huaier-induced ferroptosis can be suppressed by the autophagosome inhibitor, Wortmannin. CONCLUSION: Huaier can activate ferroptosis by inducing autophagy in PCs. Frontiers Media S.A. 2022-09-30 /pmc/articles/PMC9561879/ /pubmed/36248959 http://dx.doi.org/10.3389/fonc.2022.960858 Text en Copyright © 2022 Zhu, Wang, Zhang, Gong, Zhang, Yang, Qu, Wu, Ma, Wang and Qian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhu, Zeen
Wang, Xueni
Zhang, Wunai
Gong, Mengyuan
Zhang, Simei
Yang, Bao
Qu, Bolun
Wu, Zheng
Ma, Qingyong
Wang, Zheng
Qian, Weikun
Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
title Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
title_full Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
title_fullStr Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
title_full_unstemmed Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
title_short Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
title_sort huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561879/
https://www.ncbi.nlm.nih.gov/pubmed/36248959
http://dx.doi.org/10.3389/fonc.2022.960858
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