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Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis

Pancreatic cancer is a common gastrointestinal tract malignancy. Currently, the therapeutic strategies for pancreatic cancers include surgery, radiotherapy, and chemotherapy; however, the surgical procedure is invasive, and the overall curative outcomes are poor. Furthermore, pancreatic cancers are...

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Autores principales: Liu, Xing, Peng, Xinhui, Cen, Shuai, Yang, Cuiting, Ma, Zhijie, Shi, Xinyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992170/
https://www.ncbi.nlm.nih.gov/pubmed/36909174
http://dx.doi.org/10.3389/fphar.2023.1129662
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author Liu, Xing
Peng, Xinhui
Cen, Shuai
Yang, Cuiting
Ma, Zhijie
Shi, Xinyuan
author_facet Liu, Xing
Peng, Xinhui
Cen, Shuai
Yang, Cuiting
Ma, Zhijie
Shi, Xinyuan
author_sort Liu, Xing
collection PubMed
description Pancreatic cancer is a common gastrointestinal tract malignancy. Currently, the therapeutic strategies for pancreatic cancers include surgery, radiotherapy, and chemotherapy; however, the surgical procedure is invasive, and the overall curative outcomes are poor. Furthermore, pancreatic cancers are usually asymptomatic during early stages and have a high degree of malignancy, along with a high rate of recurrence and metastasis, thereby increasing the risk of mortality. Studies have shown that ferroptosis regulates cell proliferation and tumour growth and reduces drug resistance. Hence, ferroptosis could play a role in preventing and treating cancers. Wogonin is a flavonoid with anticancer activity against various cancers, including pancreatic cancer. It is extracted from the root of Scutellaria baicalensis Georgi. In this study, we show that wogonin inhibits the survival and proliferation of human pancreatic cancer cell lines and induces cell death. We performed RNA-sequencing and analysed the differentially expressed gene and potential molecular mechanism to determine if wogonin reduced cell survival via ferroptosis. Our results showed that wogonin upregulates the levels of Fe(2+), lipid peroxidation and superoxide and decreases the protein expression levels of ferroptosis suppressor genes, and downregulates level of glutathione in pancreatic cancer cells. In addition, ferroptosis inhibitors rescue the ferroptosis-related events induced by wogonin, thereby confirming the role of ferroptosis. A significant increase in ferroptosis-related events was observed after treatment with both wogonin and ferroptosis inducer. These results show that wogonin could significantly reduces pancreatic cancer cell proliferation and induce ferroptosis via the Nrf2/GPX4 axis. Therefore, wogonin could be potentially used for treating patients with pancreatic cancer.
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spelling pubmed-99921702023-03-09 Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis Liu, Xing Peng, Xinhui Cen, Shuai Yang, Cuiting Ma, Zhijie Shi, Xinyuan Front Pharmacol Pharmacology Pancreatic cancer is a common gastrointestinal tract malignancy. Currently, the therapeutic strategies for pancreatic cancers include surgery, radiotherapy, and chemotherapy; however, the surgical procedure is invasive, and the overall curative outcomes are poor. Furthermore, pancreatic cancers are usually asymptomatic during early stages and have a high degree of malignancy, along with a high rate of recurrence and metastasis, thereby increasing the risk of mortality. Studies have shown that ferroptosis regulates cell proliferation and tumour growth and reduces drug resistance. Hence, ferroptosis could play a role in preventing and treating cancers. Wogonin is a flavonoid with anticancer activity against various cancers, including pancreatic cancer. It is extracted from the root of Scutellaria baicalensis Georgi. In this study, we show that wogonin inhibits the survival and proliferation of human pancreatic cancer cell lines and induces cell death. We performed RNA-sequencing and analysed the differentially expressed gene and potential molecular mechanism to determine if wogonin reduced cell survival via ferroptosis. Our results showed that wogonin upregulates the levels of Fe(2+), lipid peroxidation and superoxide and decreases the protein expression levels of ferroptosis suppressor genes, and downregulates level of glutathione in pancreatic cancer cells. In addition, ferroptosis inhibitors rescue the ferroptosis-related events induced by wogonin, thereby confirming the role of ferroptosis. A significant increase in ferroptosis-related events was observed after treatment with both wogonin and ferroptosis inducer. These results show that wogonin could significantly reduces pancreatic cancer cell proliferation and induce ferroptosis via the Nrf2/GPX4 axis. Therefore, wogonin could be potentially used for treating patients with pancreatic cancer. Frontiers Media S.A. 2023-02-22 /pmc/articles/PMC9992170/ /pubmed/36909174 http://dx.doi.org/10.3389/fphar.2023.1129662 Text en Copyright © 2023 Liu, Peng, Cen, Yang, Ma and Shi. 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 Pharmacology
Liu, Xing
Peng, Xinhui
Cen, Shuai
Yang, Cuiting
Ma, Zhijie
Shi, Xinyuan
Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis
title Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis
title_full Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis
title_fullStr Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis
title_full_unstemmed Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis
title_short Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis
title_sort wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the nrf2/gpx4 axis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992170/
https://www.ncbi.nlm.nih.gov/pubmed/36909174
http://dx.doi.org/10.3389/fphar.2023.1129662
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