In:
Molecular Nutrition & Food Research, Wiley, Vol. 52, No. 6 ( 2008-06), p. 655-663
Abstract:
Geraniin, a form of tannin separated from geranium, causes cell death through induction of apoptosis; however, cell death characteristics for geraniin have not yet been elucidated. Here, we investigated the mechanism of geraniin‐induced apoptosis in human melanoma cells and demonstrated that geraniin was able to induce cell apoptosis in a concentration‐ and time‐dependent manner. We also examined the signaling pathway related to geraniin‐induced apoptosis. To clarify the relationship between focal adhesion kinase (FAK) and geraniin‐induced apoptosis, we treated human melanoma cells with geraniin and found that this resulted dose‐ and time‐dependent degradation in FAK. However, FAK cleavage was significantly inhibited when cells were pretreated with a selective inhibitor of caspase‐3 (Ac‐Asp‐Glu‐Val‐Asp‐CHO). Here, we demonstrated for the first time that geraniin triggered cell death by caspase‐3‐mediated cleavage of FAK. There were two possible mechanisms for activating caspase‐3, mitochondria‐mediated and receptor‐mediated apoptosis. To confirm the geraniin‐relevant signaling pathway, using immunoblot analysis we found that geraniin‐induced apoptosis was associated with the up‐regulation of Fas ligand expression, the activation of caspase‐8, the cleavage of Bid, and the induction of cytochrome c release from mitochondria to the cytosol. Treatment with geraniin caused induction of caspase‐3 activity in a dose‐ and time‐dependent manner followed by proteolytic cleavage of poly‐(ADP‐ribose) polymerase, and DNA fragmentation factor 45. The geraniin‐induced apoptosis may provide a pivotal mechanism for its cancer‐chemopreventive action.
Type of Medium:
Online Resource
ISSN:
1613-4125
,
1613-4133
DOI:
10.1002/mnfr.200700381
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
2160372-8
SSG:
12
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