Abstract
In our previous study, penta-acetyl geniposide ((AC)(5)GP) is suggested to induce tumor cell apoptosis through the specific activation of PKCdelta. However, the downstream signal pathway of PKCdelta has not yet been investigated. It was shown that JNK may play an important role in the regulation of apoptosis and could be a possible downstream signal of PKCdelta isoforms. In the present study, we investigate whether JNK is involved in (AC)(5)GP induced apoptosis. The result reveals that (AC)(5)GP induces JNK activation and c-Jun phosphorylation thus stimulating the expression of Fas-L and Fas. Using SP600125 to block JNK activation shows that (AC)(5)GP-mediated apoptosis and related proteins expression are attenuated. Furthermore, we find that the (AC)(5)GP induces apoptosis through the activation of JNK/Jun/Fas L/Fas/caspase 8/caspase 3, a mitochondria-independent pathway. The JNK pathway is suggested to be the downstream signal of PKCdelta, since rottlerin impedes (AC)(5)GP-induced JNK activation. Therefore, (AC)(5)GP mediates cell death via activation of PKCdelta/JNK/FasL cascade signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects*
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Caspase 3
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Caspase 8
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Caspase Inhibitors
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Caspases / drug effects
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Caspases / metabolism
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Cell Line, Tumor*
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Drug Screening Assays, Antitumor / methods
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Drugs, Chinese Herbal / chemistry
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Fas Ligand Protein
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Gardenia
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Glioma / metabolism
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Glioma / pathology
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Glucosides / chemistry
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Glucosides / isolation & purification
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Glucosides / pharmacology*
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Iridoid Glucosides
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Iridoids / chemistry
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Iridoids / isolation & purification
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Iridoids / pharmacology*
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / drug effects
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mitochondria / drug effects
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Mitochondria / physiology
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Phosphorylation
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Protein Kinase C / metabolism
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Pyrans / chemistry
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Pyrans / isolation & purification
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Pyrans / pharmacology*
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Rats
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Signal Transduction
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Taiwan
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Caspase Inhibitors
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Drugs, Chinese Herbal
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Fas Ligand Protein
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Faslg protein, rat
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Glucosides
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Iridoid Glucosides
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Iridoids
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Membrane Glycoproteins
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Pyrans
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pentaacetyl geniposide
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Protein Kinase C
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JNK Mitogen-Activated Protein Kinases
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Casp3 protein, rat
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Casp8 protein, rat
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Caspase 3
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Caspase 8
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Caspases