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Apoptosis induced by penta-acetyl geniposide in C6 glioma cells is associated with JNK activation and Fas ligand induction

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [2];  [3];  [1];  [1]
  1. Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan (China)
  2. School of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan (China)
  3. Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan (China)
In our previous study, penta-acetyl geniposide ((AC){sub 5}GP) is suggested to induce tumor cell apoptosis through the specific activation of PKC{delta}. However, the downstream signal pathway of PKC{delta} 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 PKC{delta} isoforms. In the present study, we investigate whether JNK is involved in (AC){sub 5}GP induced apoptosis. The result reveals that (AC){sub 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){sub 5}GP-mediated apoptosis and related proteins expression are attenuated. Furthermore, we find that the (AC){sub 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 PKC{delta}, since rottlerin impedes (AC){sub 5}GP-induced JNK activation. Therefore, (AC){sub 5}GP mediates cell death via activation of PKC{delta}/JNK/FasL cascade signaling.
OSTI ID:
20634836
Journal Information:
Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 202; ISSN TXAPA9; ISSN 0041-008X
Country of Publication:
United States
Language:
English

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