The ability of polyamine analogues to induce Z-DNA structure in synthetic polynucleotides in vitro inversely correlates with their effects on cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in human brain tumor cell lines

Hirak S. Basu, Malgorzata Pellarin, Burt G.F. Feuerstein, Laurence J. Marton

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Abstract

We studied the effects of 72 h pretreatment with five polyamine analogues on the cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in U-251 MG and SF-188 human brain tumor cells. A colony forming efficiency assay showed that the pretreatment with clinically important analogues 1,11-bis(ethylamino)-4,8-diazaundecane (BE-3-3-3), 1,14-bis (ethylamino)-5,10-diazatetradecane (BE-4-4-4), and 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) increased the cytotoxicity of CDDP by 1.3 to 2.3-fold; 1,19-diamino-5,10,15-triazanonadecane (4-4-4-4) did not affect CDDP cytotoxicity, and 1,11-diamino-4,8-diazaundecane (3-3-3) protected cells from the cytotoxic effects of CDDP. An alkaline elution assay detected a small increase in DNA interstrand cross-links accompanying the enhancement of CDDP cytotoxicity only in cells pretreated with BE-3-3-3. This study is the first to show that the Z-DNA inducing abilities of the polyamine analogues in synthetic polynucleotides in vitro correlates inversely with their effects on CDDP cytotoxicity in human tumor cells in culture.

Original languageEnglish (US)
Pages (from-to)39-48
Number of pages10
JournalAnticancer Research
Volume16
Issue number1
StatePublished - Jan 1996
Externally publishedYes

Fingerprint

Z-Form DNA
Polynucleotides
Polyamines
Tumor Cell Line
Brain Neoplasms
Cell Culture Techniques
DNA
N(1),N(11)-diethylnorspermine
In Vitro Techniques
Neoplasms
N(1),N(14)-bis(ethyl)homospermine
BE 4-4-4-4

Keywords

  • CDDP
  • Chromatin structure
  • DNA cross-linking
  • Z-DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "The ability of polyamine analogues to induce Z-DNA structure in synthetic polynucleotides in vitro inversely correlates with their effects on cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in human brain tumor cell lines",
abstract = "We studied the effects of 72 h pretreatment with five polyamine analogues on the cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in U-251 MG and SF-188 human brain tumor cells. A colony forming efficiency assay showed that the pretreatment with clinically important analogues 1,11-bis(ethylamino)-4,8-diazaundecane (BE-3-3-3), 1,14-bis (ethylamino)-5,10-diazatetradecane (BE-4-4-4), and 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) increased the cytotoxicity of CDDP by 1.3 to 2.3-fold; 1,19-diamino-5,10,15-triazanonadecane (4-4-4-4) did not affect CDDP cytotoxicity, and 1,11-diamino-4,8-diazaundecane (3-3-3) protected cells from the cytotoxic effects of CDDP. An alkaline elution assay detected a small increase in DNA interstrand cross-links accompanying the enhancement of CDDP cytotoxicity only in cells pretreated with BE-3-3-3. This study is the first to show that the Z-DNA inducing abilities of the polyamine analogues in synthetic polynucleotides in vitro correlates inversely with their effects on CDDP cytotoxicity in human tumor cells in culture.",
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T1 - The ability of polyamine analogues to induce Z-DNA structure in synthetic polynucleotides in vitro inversely correlates with their effects on cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in human brain tumor cell lines

AU - Basu, Hirak S.

AU - Pellarin, Malgorzata

AU - Feuerstein, Burt G.F.

AU - Marton, Laurence J.

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N2 - We studied the effects of 72 h pretreatment with five polyamine analogues on the cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in U-251 MG and SF-188 human brain tumor cells. A colony forming efficiency assay showed that the pretreatment with clinically important analogues 1,11-bis(ethylamino)-4,8-diazaundecane (BE-3-3-3), 1,14-bis (ethylamino)-5,10-diazatetradecane (BE-4-4-4), and 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) increased the cytotoxicity of CDDP by 1.3 to 2.3-fold; 1,19-diamino-5,10,15-triazanonadecane (4-4-4-4) did not affect CDDP cytotoxicity, and 1,11-diamino-4,8-diazaundecane (3-3-3) protected cells from the cytotoxic effects of CDDP. An alkaline elution assay detected a small increase in DNA interstrand cross-links accompanying the enhancement of CDDP cytotoxicity only in cells pretreated with BE-3-3-3. This study is the first to show that the Z-DNA inducing abilities of the polyamine analogues in synthetic polynucleotides in vitro correlates inversely with their effects on CDDP cytotoxicity in human tumor cells in culture.

AB - We studied the effects of 72 h pretreatment with five polyamine analogues on the cytotoxicity of cis-diaminedichloroplatinum (II) (CDDP) in U-251 MG and SF-188 human brain tumor cells. A colony forming efficiency assay showed that the pretreatment with clinically important analogues 1,11-bis(ethylamino)-4,8-diazaundecane (BE-3-3-3), 1,14-bis (ethylamino)-5,10-diazatetradecane (BE-4-4-4), and 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) increased the cytotoxicity of CDDP by 1.3 to 2.3-fold; 1,19-diamino-5,10,15-triazanonadecane (4-4-4-4) did not affect CDDP cytotoxicity, and 1,11-diamino-4,8-diazaundecane (3-3-3) protected cells from the cytotoxic effects of CDDP. An alkaline elution assay detected a small increase in DNA interstrand cross-links accompanying the enhancement of CDDP cytotoxicity only in cells pretreated with BE-3-3-3. This study is the first to show that the Z-DNA inducing abilities of the polyamine analogues in synthetic polynucleotides in vitro correlates inversely with their effects on CDDP cytotoxicity in human tumor cells in culture.

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