Linked Life Data

18804340

Source:http://linkedlifedata.com/resource/pubmed/id/18804340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-2-3
pubmed:abstractText
Platycodon D is a major constituent of triterpene saponins found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. The results of previous studies have shown that this compound has in vitro growth-inhibitory activity in human cancer cells, however, the mechanism by which this action occurs is poorly understood. In this study, we examined the effects of platycodon D on the production of reactive oxygen species (ROS) and evaluated the association of these effects with apoptotic tumor cell death using a human leukemic U937 cell line. The results of this study demonstrate that platycodon D mediates ROS production, and that this mediation is followed by a decrease in mitochondrial membrane potential (MMP, DJm), activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Both the cytotoxic effects and apoptotic characteristics induced by platycodon D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 plays in the observed cytotoxic effect. Additionally, the transcription factor early growth response-1 (Egr-1) gene was transcriptionally activated and the levels of non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) protein were elevated in platycodon D-treatedU937 cells. However, the quenching of ROS generation in response to treatment with a ROS scavenger, N-acetyl-L-cysteine, reversed the platycodon D-induced apoptosis effects via inhibition of Egr-1 activation, ROS production, MMP collapse, and the subsequent activation of caspase-3. Although further studies are needed to demonstrate that increased expression of Egr-1 by platycodon D leads directly to NAG-1 induction and subsequent apoptosis, our observations clearly indicate that ROS induced through Egr-1 activation are involved in the early molecular events involved in the platycodon D-induced apoptotic pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1950-6007
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
86-94
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Implication of intracellular ROS formation, caspase-3 activation and Egr-1 induction in platycodon D-induced apoptosis of U937 human leukemia cells.
pubmed:affiliation
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't