Polyamine analog bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) enhances simian virus 40 late gene expression

• Published in: Cancer chemotherapy and pharmacology 1999, Vol.43 (4), p.336-340
• Main Authors: BASU, H. S, DRECKSCHMIDT, N, LINH TU, CHANBUSARAKUM, L
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line; Dose-Response Relationship, Drug; Gene Expression Regulation, Viral - drug effects; General aspects; Genes, Reporter; Humans; Kinetics; Luciferases - genetics; Luciferases - metabolism; Medical sciences; Nucleosomes - drug effects; Pharmacology. Drug treatments; Propylamines - pharmacology; Recombinant Proteins - biosynthesis; Simian virus 40 - drug effects; Simian virus 40 - genetics; Spermine - analogs & derivatives; Spermine - pharmacology; Transfection; Tumor Cells, Cultured
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800050904

The polyamine analog bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) depletes cellular polyamines and inhibits malignant cell growth. We have previously shown that BE-4-4-4-4 inhibits nucleosome condensation on supercoiled DNA in a cell-free system. Here we sought to determine whether BE-4-4-4-4 inhibits nucleosome condensation in cells, and whether that effect alters the expression of specific genes. We used the simian virus 40 (SV-40) minichromosome as a model system and studied the expression of the viral late genes. It is known that the SV-40 late genes are regulated by the steroid receptor elements that, in turn, control gene expression by altering nucleosomal organization. We observed a more than six fold increase in SV-40 late gene expression in cells pretreated with BE-4-4-4-4 for 18 h. The polyamine analog bisethyl norspermine (BE-3-3-3), that does not affect nucleosomal condensation in cell free systems and has little effect on chromatin structure in cultured human tumor cells, had a negligible effect on SV-40 late gene expression under treatment conditions identical to those used with BE-4-4-4-4. Similar to the findings in the cell-free system, the polyamine analog BE-4-4-4-4 inhibited nucleosome formation and, thereby, altered the expression of specific genes in a cellular system.