Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells
Colon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., ha...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.580517/full |
| _version_ | 1819226584851152896 |
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| author | Lin Hong Lin Hong Jundixia Chen Fang Wu Fengjiao Wu Xin Shen Peisen Zheng Rongrong Shao Kongqin Lu Zhiguo Liu Daoxing Chen Guang Liang Yuepiao Cai Peng Zou Peng Zou Peng Zou Yiqun Xia |
| author_facet | Lin Hong Lin Hong Jundixia Chen Fang Wu Fengjiao Wu Xin Shen Peisen Zheng Rongrong Shao Kongqin Lu Zhiguo Liu Daoxing Chen Guang Liang Yuepiao Cai Peng Zou Peng Zou Peng Zou Yiqun Xia |
| author_sort | Lin Hong |
| collection | DOAJ |
| description | Colon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., has been reported to exert antitumor effects on several cancer cells. However, the molecular mechanisms underlying the action of ESI is still elusive. In the present study, we found that ESI potently suppressed cell proliferation in human colon cancer cells. Furthermore, our results showed that ESI treatment markedly increased cellular reactive oxygen species (ROS) levels by inhibiting thioredoxin reductase 1 (TrxR1) activity, which leads to activation of the JNK signaling pathway and eventually cell death in HCT116 and RKO cells. Importantly, we found that ESI markedly enhanced cisplatin-induced cytotoxicity in HCT116 and RKO cells. Combination of ESI and cisplatin significantly increased the production of ROS, resulting in activation of the JNK signaling pathway in HCT116 and RKO cells. In vivo, we found that ESI combined with cisplatin significantly suppressed tumor growth in HCT116 xenograft models. Together, our study provide a preclinical proof-of-concept for ESI as a potential strategy for colon cancer treatment. |
| first_indexed | 2024-12-23T10:27:49Z |
| format | Article |
| id | doaj.art-115be1b98fae44639af8bde32e3025f0 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-23T10:27:49Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-115be1b98fae44639af8bde32e3025f02022-12-21T17:50:31ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-09-01810.3389/fcell.2020.580517580517Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer CellsLin Hong0Lin Hong1Jundixia Chen2Fang Wu3Fengjiao Wu4Xin Shen5Peisen Zheng6Rongrong Shao7Kongqin Lu8Zhiguo Liu9Daoxing Chen10Guang Liang11Yuepiao Cai12Peng Zou13Peng Zou14Peng Zou15Yiqun Xia16The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaZhuji Institute of Biomedicine, School of Pharmaceutical Sciences, Wenzhou Medical University, Zhuji, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou University-Wenzhou Medical University Collaborative Innovation Center of Biomedical, Wenzhou, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, ChinaColon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., has been reported to exert antitumor effects on several cancer cells. However, the molecular mechanisms underlying the action of ESI is still elusive. In the present study, we found that ESI potently suppressed cell proliferation in human colon cancer cells. Furthermore, our results showed that ESI treatment markedly increased cellular reactive oxygen species (ROS) levels by inhibiting thioredoxin reductase 1 (TrxR1) activity, which leads to activation of the JNK signaling pathway and eventually cell death in HCT116 and RKO cells. Importantly, we found that ESI markedly enhanced cisplatin-induced cytotoxicity in HCT116 and RKO cells. Combination of ESI and cisplatin significantly increased the production of ROS, resulting in activation of the JNK signaling pathway in HCT116 and RKO cells. In vivo, we found that ESI combined with cisplatin significantly suppressed tumor growth in HCT116 xenograft models. Together, our study provide a preclinical proof-of-concept for ESI as a potential strategy for colon cancer treatment.https://www.frontiersin.org/article/10.3389/fcell.2020.580517/fullisodeoxyelephantopinoxidative stressthioredoxin reductase 1cisplatinJNK |
| spellingShingle | Lin Hong Lin Hong Jundixia Chen Fang Wu Fengjiao Wu Xin Shen Peisen Zheng Rongrong Shao Kongqin Lu Zhiguo Liu Daoxing Chen Guang Liang Yuepiao Cai Peng Zou Peng Zou Peng Zou Yiqun Xia Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells Frontiers in Cell and Developmental Biology isodeoxyelephantopin oxidative stress thioredoxin reductase 1 cisplatin JNK |
| title | Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells |
| title_full | Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells |
| title_fullStr | Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells |
| title_full_unstemmed | Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells |
| title_short | Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells |
| title_sort | isodeoxyelephantopin inactivates thioredoxin reductase 1 and activates ros mediated jnk signaling pathway to exacerbate cisplatin effectiveness in human colon cancer cells |
| topic | isodeoxyelephantopin oxidative stress thioredoxin reductase 1 cisplatin JNK |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.580517/full |
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