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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.
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Details
1 Pusan National University, Department of Integrated Biological Science, Pusan, Republic of Korea (GRID:grid.262229.f) (ISNI:0000 0001 0719 8572)
2 Pusan National University, Department of Biological Sciences, Pusan, Republic of Korea (GRID:grid.262229.f) (ISNI:0000 0001 0719 8572)
3 Korea Institute of Science and Technology (KIST), Natural Product Informatics Research Center, Gangneung, Republic of Korea (GRID:grid.35541.36) (ISNI:0000000121053345)
4 Pusan National University, Department of Integrated Biological Science, Pusan, Republic of Korea (GRID:grid.262229.f) (ISNI:0000 0001 0719 8572); Pusan National University, Department of Biological Sciences, Pusan, Republic of Korea (GRID:grid.262229.f) (ISNI:0000 0001 0719 8572); Pusan National University, Institute of Systems Biology, Pusan, Republic of Korea (GRID:grid.262229.f) (ISNI:0000 0001 0719 8572)
5 Korea Institute of Science and Technology (KIST), Natural Product Research Center, Gangneung, Republic of Korea (GRID:grid.35541.36) (ISNI:0000000121053345)