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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology*
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Cell Proliferation
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Diospyros / chemistry*
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Gene Expression Regulation, Neoplastic / drug effects*
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Hep G2 Cells
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Humans
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Liver Neoplasms / drug therapy
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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MAP Kinase Kinase 4 / genetics
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MAP Kinase Kinase 4 / metabolism
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Plant Extracts / pharmacology*
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Plant Leaves / chemistry*
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Receptor, Platelet-Derived Growth Factor beta / genetics
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Receptor, Platelet-Derived Growth Factor beta / metabolism
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Receptors, Platelet-Derived Growth Factor / genetics
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Receptors, Platelet-Derived Growth Factor / metabolism
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism
Substances
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Antineoplastic Agents, Phytogenic
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Biomarkers, Tumor
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Plant Extracts
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Receptor, Platelet-Derived Growth Factor beta
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Receptors, Platelet-Derived Growth Factor
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MAP Kinase Kinase 4
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rac GTP-Binding Proteins