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.
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,l9-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 crosslinks 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.
Basu
H S
HS
Department of Human Oncology, University of Wisconsin, Madison 53706, USA.
Pellarin
M
M
Feuerstein
B G
BG
Marton
L J
LJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D009690:Nucleic Acid Conformation; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D011073:Polyamines; C082768:BE 4-4-4-4; D013096:Spermine; D002945:Cisplatin; D013095:Spermidine