Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway
Abstract Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospy...
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doaj-ed7e5266bc9c4019bf3adc0e028a206f2020-12-08T11:51:17ZengNature Publishing GroupScientific Reports2045-23222020-10-0110111310.1038/s41598-020-75140-3Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathwayHeon-Su Kim0Jung-Soo Suh1Yoon-Kwan Jang2Sang-Hyun Ahn3Ganesan Raja4Jin-Chul Kim5Youngmi Jung6Sang Hoon Jung7Tae-Jin Kim8Department of Integrated Biological Science, Pusan National UniversityDepartment of Integrated Biological Science, Pusan National UniversityDepartment of Integrated Biological Science, Pusan National UniversityDepartment of Integrated Biological Science, Pusan National UniversityDepartment of Biological Sciences, Pusan National UniversityNatural Product Informatics Research Center, Korea Institute of Science and Technology (KIST)Department of Integrated Biological Science, Pusan National UniversityNatural Product Research Center, Korea Institute of Science and Technology (KIST)Department of Integrated Biological Science, Pusan National UniversityAbstract Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospyros kaki, leaves (EEDK) induces cancer cell death and inhibits cell proliferation. Using fluorescence resonance energy transfer (FRET) technology with genetically-encoded biosensors, we first found that EEDK stimulates a PDGFR-Rac signaling cascade in live cells. Moreover, we found that downstream of the PDGFR-Rac pathway, JNKs are activated by EEDK. In contrast, JNK-downstream inhibitors, such as CoCl2, T-5224, and pepstatin A, attenuated EEDK-induced cell death. Thus, we illustrate that the PDGFR-Rac-JNK signaling axis is triggered by EEDK, leading to cancer cell death, suggesting the extract of persimmon leaves may be a promising anti-cancer agent.https://doi.org/10.1038/s41598-020-75140-3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heon-Su Kim Jung-Soo Suh Yoon-Kwan Jang Sang-Hyun Ahn Ganesan Raja Jin-Chul Kim Youngmi Jung Sang Hoon Jung Tae-Jin Kim |
spellingShingle |
Heon-Su Kim Jung-Soo Suh Yoon-Kwan Jang Sang-Hyun Ahn Ganesan Raja Jin-Chul Kim Youngmi Jung Sang Hoon Jung Tae-Jin Kim Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway Scientific Reports |
author_facet |
Heon-Su Kim Jung-Soo Suh Yoon-Kwan Jang Sang-Hyun Ahn Ganesan Raja Jin-Chul Kim Youngmi Jung Sang Hoon Jung Tae-Jin Kim |
author_sort |
Heon-Su Kim |
title |
Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway |
title_short |
Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway |
title_full |
Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway |
title_fullStr |
Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway |
title_full_unstemmed |
Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway |
title_sort |
anti-cancer potential of persimmon (diospyros kaki) leaves via the pdgfr-rac-jnk pathway |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-10-01 |
description |
Abstract Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospyros kaki, leaves (EEDK) induces cancer cell death and inhibits cell proliferation. Using fluorescence resonance energy transfer (FRET) technology with genetically-encoded biosensors, we first found that EEDK stimulates a PDGFR-Rac signaling cascade in live cells. Moreover, we found that downstream of the PDGFR-Rac pathway, JNKs are activated by EEDK. In contrast, JNK-downstream inhibitors, such as CoCl2, T-5224, and pepstatin A, attenuated EEDK-induced cell death. Thus, we illustrate that the PDGFR-Rac-JNK signaling axis is triggered by EEDK, leading to cancer cell death, suggesting the extract of persimmon leaves may be a promising anti-cancer agent. |
url |
https://doi.org/10.1038/s41598-020-75140-3 |
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