Source:http://linkedlifedata.com/resource/pubmed/id/17188248
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2007-2-16
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pubmed:abstractText |
Based on previous evidence indicating a selective cytotoxic activity of the mixed phosphine gold complex chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) for melanoma cells, we investigated the cellular bases of its antiproliferative effect in a panel of human melanoma cell lines (JR8, SK-Mel-5, Mel-501, 2/60, 2/21 and GRIG). The drug consistently induced a dose-dependent inhibition of cell growth, with IC50 values ranging from 0.8 to 2.3 microM and, when tested under the same experimental conditions, its cytotoxic activity was higher than (from 2- to 5-fold) or comparable to that of cisplatin as a function of cell lines. The ability of the gold complex to activate programmed cell death was assessed in JR8 and 2/60 cells, and a dose-dependent increase in cells with an apoptotic nuclear morphology was observed in both cell lines (up to 40 and 66% of the overall cell population, for JR8 and 2/60 cell lines, respectively). Such an apoptotic response was mediated by a dose-dependent loss of mitochondrial membrane potential, cytochrome c and Smac/DIABLO release from mitochondria into cytosol and enhanced caspase-9 and caspase-3 catalytic activity. A reduced or completely abrogated expression of the anti-apoptotic proteins c-IAP1, XIAP and survivin in drug-treated cells was also observed. Overall, results from the study indicate that chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) markedly inhibits melanoma cell growth by inducing mitochondria-mediated apoptosis and suggest it as a good candidate for additional evaluation as an anticancer agent against melanoma.
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Organogold Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/chlorotriphenylphosphine-1,3-bis(dip...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
73
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
773-81
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pubmed:meshHeading |
pubmed-meshheading:17188248-Antineoplastic Agents,
pubmed-meshheading:17188248-Caspase 3,
pubmed-meshheading:17188248-Caspase 9,
pubmed-meshheading:17188248-Cell Line, Tumor,
pubmed-meshheading:17188248-Dose-Response Relationship, Drug,
pubmed-meshheading:17188248-Humans,
pubmed-meshheading:17188248-Melanoma,
pubmed-meshheading:17188248-Mitochondria,
pubmed-meshheading:17188248-Organogold Compounds
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pubmed:year |
2007
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pubmed:articleTitle |
Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) in melanoma cell lines.
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pubmed:affiliation |
Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche (CNR), Piazzale Aldo Moro 5, 00185 Rome, Italy. francesco.caruso@icb.cnr.it
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pubmed:publicationType |
Journal Article
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