Nuclear DNA is the target responsible for anticancer activity of platinum anticancer drugs. Their activity is mediated by altered signals related to programmed cell death and the activation of various signaling pathways. An example is activation of nuclear factor kappaB (NF-κB). Binding of NF-κB proteins to their consensus sequences in DNA (κB sites) is the key biochemical activity responsible for the biological functions of NF-κB. Using gel-mobility-shift assays and surface plasmon resonance spectroscopy we examined the interactions of NF-κB proteins with oligodeoxyribonucleotide duplexes containing κB site damaged by DNA adducts of three platinum complexes. These complexes markedly differed in their toxic effects in tumor cells and comprised highly cytotoxic trinuclear platinum(II) complex BBR3464, less cytotoxic conventional cisplatin and ineffective transplatin. The results indicate that structurally different DNA adducts of these platinum complexes exhibit a different efficiency to affect the affinity of the platinated DNA (κB sites) to NF-κB proteins. Our results support the hypothesis that structural perturbations induced in DNA by platinum(II) complexes correlate with their higher efficiency to inhibit binding of NF-κB proteins to their κB sites and cytotoxicity as well. However, the full generalization of this hypothesis will require to evaluate a larger series of platinum(II) complexes.

• MeSH
• adukty DNA chemie   metabolismus   MeSH
• cisplatina chemie   metabolismus   farmakologie   MeSH
• HEK293 buňky MeSH
• kinetika MeSH
• komplexní sloučeniny chemie   metabolismus   farmakologie   MeSH
• konsenzuální sekvence MeSH
• lidé MeSH
• NF-kappa B chemie   genetika   metabolismus   MeSH
• oligodeoxyribonukleotidy chemie   metabolismus   MeSH
• organoplatinové sloučeniny chemie   toxicita   MeSH
• platina chemie   metabolismus   MeSH
• povrchová plasmonová rezonance MeSH
• protinádorové látky chemie   metabolismus   farmakologie   MeSH
• rekombinantní proteiny biosyntéza   chemie   izolace a purifikace   MeSH
• retardační test MeSH
• termodynamika MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adukty DNA MeSH
• BBR 3464 MeSH Prohlížeč
• cisplatina MeSH
• komplexní sloučeniny MeSH
• NF-kappa B MeSH
• oligodeoxyribonukleotidy MeSH
• organoplatinové sloučeniny MeSH
• platina MeSH
• protinádorové látky MeSH
• rekombinantní proteiny MeSH