Linked Life Data

18413365

Source:http://linkedlifedata.com/resource/pubmed/id/18413365

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-7-8
pubmed:abstractText
A hallmark of cancer cells is their ability to evade apoptosis and mitochondria play a critical role in this process. Delineating mitochondrial differences between normal and cancer cells has proven challenging due to the lack of matched cell lines. Here, we compare two matched liver progenitor cell (LPC) lines, one non-tumorigenic [p53-immortalized liver (PIL) 4] and the other tumorigenic (PIL2). Analysis of these cell lines and a p53 wild-type non-tumorigenic cell line [bipotential murine oval liver (BMOL)] revealed an increase in expression of genes encoding the antiapoptotic proteins cellular inhibitor of apoptosis protein (cIAP) 1 and yes associate protein in the PIL2 cells, which resulted in an increase in the protein encoded by these genes. PIL2 cells have higher mitochondrial membrane potential (Deltapsi(m)) compared with PIL4 and BMOL and had greater levels of reactive oxygen species, despite the fact that the mitochondrial antioxidant enzyme, manganese superoxide disumutase, was elevated at transcript and protein levels. Taken together, these results may account for the observed resistance of PIL2 cells to apoptotic stimuli compared with PIL4. We tested a new gold compound to show that hyperpolarized Deltapsi(m) led to its increased accumulation in mitochondria of PIL2 cells. This compound selectively induces apoptosis in PIL2 cells but not in PIL4 or BMOL. The gold compound depolarized the Deltapsi(m), depleted the adenosine triphosphate pool and activated caspase-3 and caspase-9, suggesting that apoptosis was mediated via mitochondria. This investigation shows that the non-tumorigenic and tumorigenic LPCs are useful models to delineate the role of mitochondrial dysfunction in tumorigenesis and for the future development of mitochondria-targeted chemotherapeutics that selectively target tumor cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1124-33
pubmed:meshHeading
pubmed-meshheading:18413365-Adaptor Proteins, Signal Transducing, pubmed-meshheading:18413365-Animals, pubmed-meshheading:18413365-Antineoplastic Agents, pubmed-meshheading:18413365-Apoptosis, pubmed-meshheading:18413365-Cell Line, Tumor, pubmed-meshheading:18413365-Drug Resistance, Neoplasm, pubmed-meshheading:18413365-Energy Metabolism, pubmed-meshheading:18413365-Gene Expression, pubmed-meshheading:18413365-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18413365-Gold Compounds, pubmed-meshheading:18413365-Hepatocytes, pubmed-meshheading:18413365-Immunoblotting, pubmed-meshheading:18413365-Inhibitor of Apoptosis Proteins, pubmed-meshheading:18413365-Membrane Potential, Mitochondrial, pubmed-meshheading:18413365-Mice, pubmed-meshheading:18413365-Microarray Analysis, pubmed-meshheading:18413365-Mitochondria, pubmed-meshheading:18413365-Phosphoproteins, pubmed-meshheading:18413365-Reactive Oxygen Species, pubmed-meshheading:18413365-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18413365-Stem Cells
pubmed:year
2008
pubmed:articleTitle
Bioenergetic differences selectively sensitize tumorigenic liver progenitor cells to a new gold(I) compound.
pubmed:affiliation
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Center for Medical Research, The University of Western Australia, Perth, Western Australia 6000, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't