Apoptosis and inhibition of gap-junctional intercellular communication induced by LA-12, a novel hydrophobic platinum(IV) complex
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
17466256
DOI
10.1016/j.abb.2007.03.021
PII: S0003-9861(07)00150-6
Knihovny.cz E-zdroje
- MeSH
- amantadin analogy a deriváty farmakologie MeSH
- antitumorózní látky farmakologie MeSH
- apoptóza * MeSH
- buněčné linie MeSH
- cisplatina farmakologie MeSH
- epitelové buňky metabolismus MeSH
- fosforylace MeSH
- hydrofobní a hydrofilní interakce MeSH
- konexin 43 metabolismus MeSH
- krysa rodu Rattus MeSH
- mezerový spoj účinky léků MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny farmakologie MeSH
- sloučeniny platiny chemie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amantadin MeSH
- antitumorózní látky MeSH
- bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) MeSH Prohlížeč
- cisplatina MeSH
- konexin 43 MeSH
- organoplatinové sloučeniny MeSH
- sloučeniny platiny MeSH
A new hydrophobic platinum(IV) complex, LA-12, a very efficient anticancer drug lacking cross-resistance with cisplatin (CDDP), is now being tested in clinical trials. Here we investigated the apoptogenic activity of LA-12 and its effect on gap-junctional intercellular communication (GJIC) in the rat liver epithelial cell line WB-F344. LA-12 induced apoptosis much more efficiently than did CDDP due to a combination of rapid penetration into the cell and attack on DNA, leading to fast activation of p53 and caspase-3. Exposure of WB-F344 cells to LA-12 led to rapid induction of the time- and dose-dependent decrease in GJIC. On the molecular level, loss of GJIC induced by LA-12 was mediated by activation of extracellular signal-regulated kinase (ERK)-1 and ERK-2, as demonstrated by the use of inhibitors of ERK activation. Inhibition of GJIC was linked to rapid hyperphosphorylation of connexin-43 and disappearance of connexon clusters from membranes, which was not observed in the case of CDDP.
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