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Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro

SIMPLE SUMMARY: Scabertopin is one of the major sesquiterpene lactones from Elephantopus scaber L. Sesquiterpene lactones are thought to have fairly strong anti-cancer efficacy. However, there has not been any research report on the efficacy and mechanism of Scabertopin in the treatment of bladder c...

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Autores principales: Gao, Yuanhui, Nie, Zhenyu, Cao, Hui, Huang, Denggao, Chen, Mei, Xiang, Yang, Yu, Xiaolong, Zhang, Shufang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738305/
https://www.ncbi.nlm.nih.gov/pubmed/36497458
http://dx.doi.org/10.3390/cancers14235976
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author Gao, Yuanhui
Nie, Zhenyu
Cao, Hui
Huang, Denggao
Chen, Mei
Xiang, Yang
Yu, Xiaolong
Zhang, Shufang
author_facet Gao, Yuanhui
Nie, Zhenyu
Cao, Hui
Huang, Denggao
Chen, Mei
Xiang, Yang
Yu, Xiaolong
Zhang, Shufang
author_sort Gao, Yuanhui
collection PubMed
description SIMPLE SUMMARY: Scabertopin is one of the major sesquiterpene lactones from Elephantopus scaber L. Sesquiterpene lactones are thought to have fairly strong anti-cancer efficacy. However, there has not been any research report on the efficacy and mechanism of Scabertopin in the treatment of bladder cancer. The aim of this study is to evaluate the antitumor activity of scabertopin in bladder cancer and its potential molecular mechanism in vitro. In this study, we found that scabertopin can induce necroptosis in bladder cancer cells by promoting the production of mitochondrial reactive oxygen species, and also inhibit the migration and invasion ability of bladder cancer cells. At the same time, we also demonstrated that the half-inhibition rate of scabertopin on various bladder cancer cell lines is much lower than that on human ureteral epithelial immortalized cells. This shows that scabertopin is a safe and effective anti-bladder cancer drug. ABSTRACT: Bladder cancer remains one of the most common malignant tumors that threatens human health worldwide. It imposes a heavy burden on patients and society due to the high medical costs associated with its easy metastasis and recurrence. Although several treatment options for bladder cancer are available, their clinical efficacy remains unsatisfactory. Therefore, actively exploring new drugs and their mechanisms of action for the clinical treatment of bladder cancer is very important. Scabertopin is one of the major sesquiterpene lactones found in Elephantopus scaber L. Sesquiterpene lactones are thought to have fairly strong anti-cancer efficacy. However, the anticancer effect of sesquiterpenoid scabertopin on bladder cancer and its mechanism are still unclear. The aim of this study is to evaluate the antitumor activity of scabertopin in bladder cancer and its potential molecular mechanism in vitro. Our results suggest that scabertopin can induce RIP1/RIP3-dependent necroptosis in bladder cancer cells by promoting the production of mitochondrial reactive oxygen species (ROS), inhibit the expression of MMP-9 by inhibiting the FAK/PI3K/Akt signaling pathway, and ultimately inhibit the migration and invasion ability of bladder cancer cells. At the same time, we also demonstrated that the half-inhibition concentration (IC50) of scabertopin on various bladder cancer cell lines (J82, T24, RT4 and 5637) is much lower than that on human ureteral epithelial immortalized cells (SV-HUC-1). The above observations indicate that scabertopin is a potential therapeutic agent for bladder cancer that acts by inducing necroptosis and inhibiting metastasis.
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spelling pubmed-97383052022-12-11 Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro Gao, Yuanhui Nie, Zhenyu Cao, Hui Huang, Denggao Chen, Mei Xiang, Yang Yu, Xiaolong Zhang, Shufang Cancers (Basel) Article SIMPLE SUMMARY: Scabertopin is one of the major sesquiterpene lactones from Elephantopus scaber L. Sesquiterpene lactones are thought to have fairly strong anti-cancer efficacy. However, there has not been any research report on the efficacy and mechanism of Scabertopin in the treatment of bladder cancer. The aim of this study is to evaluate the antitumor activity of scabertopin in bladder cancer and its potential molecular mechanism in vitro. In this study, we found that scabertopin can induce necroptosis in bladder cancer cells by promoting the production of mitochondrial reactive oxygen species, and also inhibit the migration and invasion ability of bladder cancer cells. At the same time, we also demonstrated that the half-inhibition rate of scabertopin on various bladder cancer cell lines is much lower than that on human ureteral epithelial immortalized cells. This shows that scabertopin is a safe and effective anti-bladder cancer drug. ABSTRACT: Bladder cancer remains one of the most common malignant tumors that threatens human health worldwide. It imposes a heavy burden on patients and society due to the high medical costs associated with its easy metastasis and recurrence. Although several treatment options for bladder cancer are available, their clinical efficacy remains unsatisfactory. Therefore, actively exploring new drugs and their mechanisms of action for the clinical treatment of bladder cancer is very important. Scabertopin is one of the major sesquiterpene lactones found in Elephantopus scaber L. Sesquiterpene lactones are thought to have fairly strong anti-cancer efficacy. However, the anticancer effect of sesquiterpenoid scabertopin on bladder cancer and its mechanism are still unclear. The aim of this study is to evaluate the antitumor activity of scabertopin in bladder cancer and its potential molecular mechanism in vitro. Our results suggest that scabertopin can induce RIP1/RIP3-dependent necroptosis in bladder cancer cells by promoting the production of mitochondrial reactive oxygen species (ROS), inhibit the expression of MMP-9 by inhibiting the FAK/PI3K/Akt signaling pathway, and ultimately inhibit the migration and invasion ability of bladder cancer cells. At the same time, we also demonstrated that the half-inhibition concentration (IC50) of scabertopin on various bladder cancer cell lines (J82, T24, RT4 and 5637) is much lower than that on human ureteral epithelial immortalized cells (SV-HUC-1). The above observations indicate that scabertopin is a potential therapeutic agent for bladder cancer that acts by inducing necroptosis and inhibiting metastasis. MDPI 2022-12-02 /pmc/articles/PMC9738305/ /pubmed/36497458 http://dx.doi.org/10.3390/cancers14235976 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Yuanhui
Nie, Zhenyu
Cao, Hui
Huang, Denggao
Chen, Mei
Xiang, Yang
Yu, Xiaolong
Zhang, Shufang
Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro
title Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro
title_full Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro
title_fullStr Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro
title_full_unstemmed Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro
title_short Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro
title_sort scabertopin derived from elephantopus scaber l. mediates necroptosis by inducing reactive oxygen species production in bladder cancer in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738305/
https://www.ncbi.nlm.nih.gov/pubmed/36497458
http://dx.doi.org/10.3390/cancers14235976
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