PubMed · 11376435
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J M Opitz, E B Clark. 2000. Heart development: an introduction.. https://pubmed.ncbi.nlm.nih.gov/11376435/
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The crude dichloromethane bark extract of Pilidiostigma tropicum (Myrtaceae) from north Queensland, Australia, shows antibacterial and cytotoxic activity. Bioactivity-directed separation led to the isolation of rhodomyrtoxin B and ursolic acid-3-p-coumarate as the biologically active materials. The structures of these compounds were elucidated on the basis of spectral analysis. The intercalation interaction of rhodomyrtoxin B with DNA was investigated using molecular mechanics and ab initio molecular-orbital techniques. A favorable pi-pi interaction between rhodomyrtoxin B and the cytosine-guanine base pair is predicted, but the orientation of the interaction cannot be predicted based on frontier molecular orbitals.
Nucleolin associates with various DNA repair, recombination, and replication proteins, and possesses DNA helicase, strand annealing, and strand pairing activities. Examination of nuclear protein extracts from human somatic cells revealed that nucleolin and Rad51 co-immunoprecipitate. Furthermore, purified recombinant Rad51 associates with in vitro transcribed and translated nucleolin. Electroporation-mediated introduction of anti-nucleolin antibody resulted in a 10- to 20-fold reduction in intra-plasmid homologous recombination activity in human fibrosarcoma cells. Additionally, introduction of anti-nucleolin antibody sensitized cells to death induced by the topoisomerase II inhibitor, amsacrine. Introduction of anti-Rad51 antibody also reduced intra-plasmid homologous recombination activity and induced hypersensitivity to amsacrine-induced cell death. Co-introduction of anti-nucleolin and anti-Rad51 antibodies did not produce additive effects on homologous recombination or on cellular sensitivity to amsacrine. The association of the two proteins raises the intriguing possibility that nucleolin binding to Rad51 may function to regulate homologous recombinational repair of chromosomal DNA.
Digitoxin is used in the treatment of cardiac congestion and some types of cardiac arrhythmias. The mechanism of action of this cardiac glycoside suggested that it might antagonize the anticancer activity of topoisomerase II poisons. The present report shows that digitoxin, at concentrations commonly found in the plasma of cardiac patients, significantly reduced etoposide and idarubicin-induced topoisomerase II cleavable complexes in K562 leukemia cells. This may lead to a reduction in the anticancer effect of these two topoisomerase II poisons when they are used in the clinic concurrently with digitoxin.