Effects of vanadium complexes on cell growth of human leukemia cells and protein-DNA interactions.
Vanadium complexes are known to possess potent insulin-mimetic effects, high affinity for several enzymes and anticancer activity, which deserve increasing attention for application to biomedical sciences. Different vanadium complexes have been found to be more effective than the simple vanadium-(IV) and -(V) salts in experiments performed both in vitro and in vivo. Application of polyoxometalates as potential drugs against Herpes Simplex Virus and AIDS have also increased the interest to study the association between vanadium containing species and proteins. The aim of our research was to investigate the in vitro antiproliferative activity of a variety of vanadium-containing compounds, and study their ability to interfere with the molecular interactions between GATA-1 and NF-kappaB transcription factors and target DNA elements, employing electrophoretic mobility shift assays. All of the used vanadium compounds were found to exhibit antiproliferative activity, despite with differences in efficacy. Inhibition of K562 cell growth was not associated with differentiation, but with activation of apoptosis. Vanadium complexes with a +5 oxidation state and their discrete anionic units appear essential for the respective effects on K562 cells; a +4 oxidation state appears to be important in inhibiting transcription factors/DNA interactions.
Lampronti
Ilaria
I
ER-GenTech, Department of Biochemistry and Molecular Biology, Section of Molecular Biology, Ferrara University, Ferrara, Italy.
Bianchi
Nicoletta
N
Borgatti
Monica
M
Fabbri
Enrica
E
Vizziello
Leonardo
L
Khan
Mahmud Tareq Hassan
MT
Ather
Arjumand
A
Brezena
Dan
D
Tahir
Mohammad Mahroof
MM
Gambari
Roberto
R
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D017968:Vanadium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D017968:Vanadium Compounds