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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Main Authors: 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
Format: Article
Language:English
Published: Nature Publishing Group 2020-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-75140-3
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spelling 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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