Linked Life Data

17512508

Source:http://linkedlifedata.com/resource/pubmed/id/17512508

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-6-18
pubmed:abstractText
The central objective of the current study was to investigate the potential in vitro anti-proliferative properties of the parent ligand, coumarin-dioxy-acetic acid (cdoaH(2)), and its copper complex, copper-coumarin-dioxyacetic acetate-phenathroline ([Cu(cdoa)(phen)(2)]) using four human-derived model cell lines, two neoplastic and two non-neoplastic. In addition, selected mechanistic studies were carried out using one of the neoplastic-derived model cell lines, Hep-G2. Results obtained show that the complex, rather than the ligand, could alter the proliferation of both human neoplastic renal (A-498) and hepatic (Hep-G2) cells. Furthermore, hepatic non-neoplastic cells (Chang) appeared to be less sensitive. However, this effect was not mirrored in non-neoplastic renal (HK-2) cells, a profile shared with cisplatin. The observed anti-proliferative effect appeared to be concentration- and time-dependant, and could be attributed to the complex, rather than any of the component parts, i.e. 1,10-phenanthroline, the coumarin ligand, or the simple metal salt. Furthermore, the complex was shown to decrease DNA synthesis, but did not intercalate with it. Based on IC(50) values, [Cu(cdoa)(phen)(2)] was shown to be almost six times more potent than cisplatin. Moreover, there was no evidence to show that P-glycoprotein (P-gp)-mediated multi-drug resistance (MDR) was likely to play a role in decreasing the anti-proliferative activity of the complex. Cytological stains, analysis of genomic DNA, and biochemical assays [caspase-3 and -9 and cleaved poly(ADP-ribose)-polymerase protein], suggested that cell death could switch between apoptosis and necrosis, and this effect appeared to be concentration-dependent. Additionally, flow cytometric analysis showed that the complex functioned through an alteration in cell cycle progression. Taken together, [Cu(cdoa)(phen)(2)] has been shown to be a more potent anti-proliferative agent than either the ligand or cisplatin, and is capable of altering key biochemical events leading to the execution of apoptotic and/or necrotic cell death, suggesting that it is worthy of further investigation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0009-2797
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-58
pubmed:meshHeading
pubmed-meshheading:17512508-Animals, pubmed-meshheading:17512508-Antineoplastic Agents, pubmed-meshheading:17512508-Apoptosis, pubmed-meshheading:17512508-CHO Cells, pubmed-meshheading:17512508-Caspases, pubmed-meshheading:17512508-Cell Cycle, pubmed-meshheading:17512508-Cell Line, Tumor, pubmed-meshheading:17512508-Cell Proliferation, pubmed-meshheading:17512508-Copper, pubmed-meshheading:17512508-Coumarins, pubmed-meshheading:17512508-Cricetinae, pubmed-meshheading:17512508-Cricetulus, pubmed-meshheading:17512508-DNA, Neoplasm, pubmed-meshheading:17512508-DNA Replication, pubmed-meshheading:17512508-Dose-Response Relationship, Drug, pubmed-meshheading:17512508-Humans, pubmed-meshheading:17512508-Neoplasms, pubmed-meshheading:17512508-Organometallic Compounds, pubmed-meshheading:17512508-P-Glycoprotein, pubmed-meshheading:17512508-Phenanthrolines
pubmed:year
2007
pubmed:articleTitle
An in vitro investigation of the induction of apoptosis and modulation of cell cycle events in human cancer cells by bisphenanthroline-coumarin-6,7-dioxacetatocopper(II) complex.
pubmed:affiliation
Centre for Pharmaceutical Research & Development, Institute of Technology, Tallaght, Dublin 24, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't