Comparison of the effects of treatment with the polyamine analogue N1,N8bis(ethyl)spermidine (BESpd) or difluoromethylornithine (DFMO) on the topoisomerase II mediated formation of 4′-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) induced cleavable complex in the human lung carcinoma line NCI H157

Steven C. Denstman, Stephanie J. Ervin, Robert A Casero

Research output: Contribution to journalArticle

Abstract

The positively charged polyamines putrescine, spermidine, and spermine are thought to be important in the maintenance of chromosomal structure. Polyamine depletion by the ornithine decarboxylase inhibitor, 2-difluoromethyl-ornithine (DFMO) is known to alter the effect of several DNA active agents, presumably resulting from the altered conformation of the polyamine depleted DNa. Here we compare the polyamine depletion effects of DFMO and the spermidine analogue N1,N8 bis(ethyl)spermidine (BESpd) on the formation of Topoisomerase II mediated, 4′-(9-acridinylamino) methane-sulfon-m-anisidide (m-AMSA) induced cleavable complex formation in human large cell undifferentiated lung carcinoma NCI H157 cells. This human cell line responds in the normal cytostatic manner to DFMO, whereas it responds in an unusual cytotoxic manner to treatment with BESpd. Here we report that neither DFMO nor BESpd alone affects the formation of cleavable complex. However, both compounds significantly enhance the m-AMSA induced formation of cleavable complex, each by approximately 1.6 fold. These results indicate that both DFMO and BESpd lead to a similar depletion of nuclear polyamines. Additionally, although BESpd closely resembles the natural polyamine spermidine, it appears that it cannot substitute for Spd at the level of DNA.

Original languageEnglish (US)
Pages (from-to)194-202
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume149
Issue number1
DOIs
StatePublished - Nov 30 1987

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Eflornithine
Type II DNA Topoisomerase
Spermidine
Methane
Polyamines
Carcinoma
Lung
Putrescine
Spermine
DNA
Cytostatic Agents
Conformations
Cells
Maintenance
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Comparison of the effects of treatment with the polyamine analogue N1,N8bis(ethyl)spermidine (BESpd) or difluoromethylornithine (DFMO) on the topoisomerase II mediated formation of 4′-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) induced cleavable complex in the human lung carcinoma line NCI H157",
abstract = "The positively charged polyamines putrescine, spermidine, and spermine are thought to be important in the maintenance of chromosomal structure. Polyamine depletion by the ornithine decarboxylase inhibitor, 2-difluoromethyl-ornithine (DFMO) is known to alter the effect of several DNA active agents, presumably resulting from the altered conformation of the polyamine depleted DNa. Here we compare the polyamine depletion effects of DFMO and the spermidine analogue N1,N8 bis(ethyl)spermidine (BESpd) on the formation of Topoisomerase II mediated, 4′-(9-acridinylamino) methane-sulfon-m-anisidide (m-AMSA) induced cleavable complex formation in human large cell undifferentiated lung carcinoma NCI H157 cells. This human cell line responds in the normal cytostatic manner to DFMO, whereas it responds in an unusual cytotoxic manner to treatment with BESpd. Here we report that neither DFMO nor BESpd alone affects the formation of cleavable complex. However, both compounds significantly enhance the m-AMSA induced formation of cleavable complex, each by approximately 1.6 fold. These results indicate that both DFMO and BESpd lead to a similar depletion of nuclear polyamines. Additionally, although BESpd closely resembles the natural polyamine spermidine, it appears that it cannot substitute for Spd at the level of DNA.",
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T1 - Comparison of the effects of treatment with the polyamine analogue N1,N8bis(ethyl)spermidine (BESpd) or difluoromethylornithine (DFMO) on the topoisomerase II mediated formation of 4′-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) induced cleavable complex in the human lung carcinoma line NCI H157

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AU - Ervin, Stephanie J.

AU - Casero, Robert A

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N2 - The positively charged polyamines putrescine, spermidine, and spermine are thought to be important in the maintenance of chromosomal structure. Polyamine depletion by the ornithine decarboxylase inhibitor, 2-difluoromethyl-ornithine (DFMO) is known to alter the effect of several DNA active agents, presumably resulting from the altered conformation of the polyamine depleted DNa. Here we compare the polyamine depletion effects of DFMO and the spermidine analogue N1,N8 bis(ethyl)spermidine (BESpd) on the formation of Topoisomerase II mediated, 4′-(9-acridinylamino) methane-sulfon-m-anisidide (m-AMSA) induced cleavable complex formation in human large cell undifferentiated lung carcinoma NCI H157 cells. This human cell line responds in the normal cytostatic manner to DFMO, whereas it responds in an unusual cytotoxic manner to treatment with BESpd. Here we report that neither DFMO nor BESpd alone affects the formation of cleavable complex. However, both compounds significantly enhance the m-AMSA induced formation of cleavable complex, each by approximately 1.6 fold. These results indicate that both DFMO and BESpd lead to a similar depletion of nuclear polyamines. Additionally, although BESpd closely resembles the natural polyamine spermidine, it appears that it cannot substitute for Spd at the level of DNA.

AB - The positively charged polyamines putrescine, spermidine, and spermine are thought to be important in the maintenance of chromosomal structure. Polyamine depletion by the ornithine decarboxylase inhibitor, 2-difluoromethyl-ornithine (DFMO) is known to alter the effect of several DNA active agents, presumably resulting from the altered conformation of the polyamine depleted DNa. Here we compare the polyamine depletion effects of DFMO and the spermidine analogue N1,N8 bis(ethyl)spermidine (BESpd) on the formation of Topoisomerase II mediated, 4′-(9-acridinylamino) methane-sulfon-m-anisidide (m-AMSA) induced cleavable complex formation in human large cell undifferentiated lung carcinoma NCI H157 cells. This human cell line responds in the normal cytostatic manner to DFMO, whereas it responds in an unusual cytotoxic manner to treatment with BESpd. Here we report that neither DFMO nor BESpd alone affects the formation of cleavable complex. However, both compounds significantly enhance the m-AMSA induced formation of cleavable complex, each by approximately 1.6 fold. These results indicate that both DFMO and BESpd lead to a similar depletion of nuclear polyamines. Additionally, although BESpd closely resembles the natural polyamine spermidine, it appears that it cannot substitute for Spd at the level of DNA.

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