Source:http://linkedlifedata.com/resource/pubmed/id/18762247
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2008-12-8
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| pubmed:abstractText |
Evidence that curcumin may have anticancer activities has renewed interest in its potential to prevent and treat disease. In this study, we show that curcumin-mediated rapid generation of reactive oxygen species (ROS) leads to apoptosis by modulating different apoptotic pathways in mouse fibroblast L929 cells. We show for the first time that curcumin-induced rapid ROS generation causes the release of apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus, hence, leading to caspase 3-independent apoptosis. However, our studies also show that curcumin induces the release of cytochrome c from mitochondria, causing activation of caspase 3, and concomitant PARP cleavage, which is the hallmark of caspase-dependent apoptosis. Furthermore, curcumin-induced ROS generation leads to the induction of the proapoptotic protein p53 and its effector protein p21 and down-regulation of cell cycle regulatory proteins such as Rb and cyclin D1 and D3. Both glutathione (GSH) and N-acetylcysteine (NAC) pretreatment resulted in the complete inhibition of curcumin-induced ROS generation, AIF release from mitochondria, and caspase activation. Additionally, pretreatment of L929 cells with these antioxidants completely blocked the induction of p53-dependent p21 accumulation. In conclusion, our data show that in addition to caspase 3 activation, curcumin-induced rapid ROS generation leads to AIF release, and the activation of the caspase-independent apoptotic pathway.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Chloromethyl Ketones,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Curcumin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylvalyl-alanyl-aspart...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0891-5849
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
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| pubmed:volume |
45
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1403-12
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| pubmed:meshHeading |
pubmed-meshheading:18762247-Amino Acid Chloromethyl Ketones,
pubmed-meshheading:18762247-Animals,
pubmed-meshheading:18762247-Antioxidants,
pubmed-meshheading:18762247-Apoptosis,
pubmed-meshheading:18762247-Caspase 3,
pubmed-meshheading:18762247-Cell Cycle Proteins,
pubmed-meshheading:18762247-Cell Line,
pubmed-meshheading:18762247-Cell Survival,
pubmed-meshheading:18762247-Curcumin,
pubmed-meshheading:18762247-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:18762247-Cytochromes c,
pubmed-meshheading:18762247-Dose-Response Relationship, Drug,
pubmed-meshheading:18762247-Mice,
pubmed-meshheading:18762247-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:18762247-Reactive Oxygen Species,
pubmed-meshheading:18762247-Time Factors,
pubmed-meshheading:18762247-Tumor Suppressor Protein p53
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| pubmed:year |
2008
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| pubmed:articleTitle |
Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells.
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| pubmed:affiliation |
Cell Signaling Laboratory, Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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