Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells
Libertellenone H (LH), a marine-derived pimarane diterpenoid isolated from arctic fungus Eutypella sp. D-1, has shown effective cytotoxicity on a range of cancer cells. The present study is to explore the anticancer effect of LH on human pancreatic cancer cells and to investigate the intracellular m...
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ftmdpi:oai:mdpi.com:/1420-3049/26/2/315/ 2023-08-20T04:04:37+02:00 Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells Weirui Zhang Yuping Zhu Haobing Yu Xiaoyu Liu Binghua Jiao Xiaoling Lu agris 2021-01-09 application/pdf https://doi.org/10.3390/molecules26020315 EN eng Multidisciplinary Digital Publishing Institute Natural Products Chemistry https://dx.doi.org/10.3390/molecules26020315 https://creativecommons.org/licenses/by/4.0/ Molecules; Volume 26; Issue 2; Pages: 315 Libertellenone H pancreatic cancer ROS Trx system apoptosis Text 2021 ftmdpi https://doi.org/10.3390/molecules26020315 2023-08-01T00:50:05Z Libertellenone H (LH), a marine-derived pimarane diterpenoid isolated from arctic fungus Eutypella sp. D-1, has shown effective cytotoxicity on a range of cancer cells. The present study is to explore the anticancer effect of LH on human pancreatic cancer cells and to investigate the intracellular molecular target and underlying mechanism. As shown, LH exhibited anticancer activity in human pancreatic cancer cells by promoting cell apoptosis. Mechanistic studies suggested that LH-induced reactive oxygen species (ROS) accumulation was responsible for apoptosis as antioxidant N-acetylcysteine (NAC) and antioxidant enzyme superoxide dismutase (SOD) antagonized the inhibitory effect of LH. Zymologic testing demonstrated that LH inhibited Trx system but had little effect on the glutathione reductase and glutaredoxin. Mass spectrometry (MS) analysis revealed that the mechanism of action was based on the direct conjugation of LH to the Cys32/Cys35 residue of Trx1 and Sec498 of TrxR, leading to a decrease in the cellular level of glutathione (GSH) and activation of downstream ASK1/JNK signaling pathway. Taken together, our findings revealed LH was a marine derived inhibitor of Trx system and an anticancer candidate. Text Arctic MDPI Open Access Publishing Arctic Molecules 26 2 315 |
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English |
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Libertellenone H pancreatic cancer ROS Trx system apoptosis |
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Libertellenone H pancreatic cancer ROS Trx system apoptosis Weirui Zhang Yuping Zhu Haobing Yu Xiaoyu Liu Binghua Jiao Xiaoling Lu Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells |
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Libertellenone H pancreatic cancer ROS Trx system apoptosis |
description |
Libertellenone H (LH), a marine-derived pimarane diterpenoid isolated from arctic fungus Eutypella sp. D-1, has shown effective cytotoxicity on a range of cancer cells. The present study is to explore the anticancer effect of LH on human pancreatic cancer cells and to investigate the intracellular molecular target and underlying mechanism. As shown, LH exhibited anticancer activity in human pancreatic cancer cells by promoting cell apoptosis. Mechanistic studies suggested that LH-induced reactive oxygen species (ROS) accumulation was responsible for apoptosis as antioxidant N-acetylcysteine (NAC) and antioxidant enzyme superoxide dismutase (SOD) antagonized the inhibitory effect of LH. Zymologic testing demonstrated that LH inhibited Trx system but had little effect on the glutathione reductase and glutaredoxin. Mass spectrometry (MS) analysis revealed that the mechanism of action was based on the direct conjugation of LH to the Cys32/Cys35 residue of Trx1 and Sec498 of TrxR, leading to a decrease in the cellular level of glutathione (GSH) and activation of downstream ASK1/JNK signaling pathway. Taken together, our findings revealed LH was a marine derived inhibitor of Trx system and an anticancer candidate. |
format |
Text |
author |
Weirui Zhang Yuping Zhu Haobing Yu Xiaoyu Liu Binghua Jiao Xiaoling Lu |
author_facet |
Weirui Zhang Yuping Zhu Haobing Yu Xiaoyu Liu Binghua Jiao Xiaoling Lu |
author_sort |
Weirui Zhang |
title |
Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells |
title_short |
Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells |
title_full |
Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells |
title_fullStr |
Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells |
title_full_unstemmed |
Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells |
title_sort |
libertellenone h, a natural pimarane diterpenoid, inhibits thioredoxin system and induces ros-mediated apoptosis in human pancreatic cancer cells |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2021 |
url |
https://doi.org/10.3390/molecules26020315 |
op_coverage |
agris |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Molecules; Volume 26; Issue 2; Pages: 315 |
op_relation |
Natural Products Chemistry https://dx.doi.org/10.3390/molecules26020315 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/molecules26020315 |
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Molecules |
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26 |
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2 |
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315 |
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