Linked Life Data

1898982

Source:http://linkedlifedata.com/resource/pubmed/id/1898982

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-2-19
pubmed:abstractText
Bis(diphenylphosphine)ethane (DPPE) and its gold coordination complexes have demonstrated antitumor activity in transplantable tumor models. This report describes the development of a P388 cell line (P388/DPPEc) that is resistant to DPPE and its analogues and the in vitro characterization of the cross-resistance of this subline to various antitumor and cytotoxic agents. The P388/DPPE tumor cell line was developed by serial transplantation in DPPE-treated mice. Resistance to DPPE was phenotypically stable. The P388/DPPE subline was cross-resistant to DPPE analogues and metal coordination complexes of DPPE. In addition, P388/DPPE cells were resistant to several mitochondrial uncouplers, including rhodamine-123, tetraphenylphosphonium, and carbonylcyanide-p-trifluro-methoxyphenyl hydrazone. P388/DPPE cells were less capable of sequestering and retaining 123Rh than were sensitive (P388/S) cells. Exposure to Au(DPPE)2+, a gold complex of DPPE with increased antitumor activity, resulted in a depletion of cellular ATP; the depletion was more rapid in the sensitive than the resistant cells. The rate of mitochondrial respiration, as measured by 14CO2 evolution from [6-14C]glucose, was greater in P388/S than in P388/DPPE. As with that evidenced for 123Rh, the cellular uptake of radiolabeled DPPE was decreased in P388/DPPEc cells. The results suggest that the basis for the resistance of this cell line may be an alteration in mitochondrial membrane potential. These data and the striking cross-resistance of P388/DPPE to mitochondrial uncouplers support the hypothesis that mitochondria may be one target involved in the cytotoxic or antitumor activities of these compounds. Mitochondria may also be causally related to the cytotoxic or antitumor activities, in that DPPE may be concentrated in cells via the presence of the inner mitochondrial membrane potential. Thus, P388/DPPE cells can serve as a tool to screen for and evaluate drugs that rely on affecting mitochondrial function, either mechanistically or causally, for their antitumor efficacy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Carbon Dioxide, http://linkedlifedata.com/resource/pubmed/chemical/Gold, http://linkedlifedata.com/resource/pubmed/chemical/Organogold Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Organometallic Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Rhodamine 123, http://linkedlifedata.com/resource/pubmed/chemical/Rhodamines, http://linkedlifedata.com/resource/pubmed/chemical/bis(1,2-bis(diphenylphosphino)ethane..., http://linkedlifedata.com/resource/pubmed/chemical/bis(diphenylphosphine)ethane
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
90-7
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
In vivo development and in vitro characterization of a subclone of murine P388 leukemia resistant to bis(diphenylphosphine)ethane.
pubmed:affiliation
SmithKline and French Research and Development Laboratories, King of Prussia, Pennsylvania 19406.
pubmed:publicationType
Journal Article