Differences in the topoisomerase I cleavage complexes formed by camptothecin and wakayin, a DNA-intercalating marine natural product.
Wakayin is bispyrroloiminoquinone isolated from a Clavelina sp. ascidian by cytotoxicity directed fractionation. Like camptothecin, it has been found to inhibit the topoisomerase I catalyzed relaxation of supercoiled DNA. Wakayin enhanced cleavage complex formation at the same DNA sequences as camptothecin. Both compounds showed dose-related increases in cleavage complex formation, though wakayin's effect is attenuated at high concentrations. Wakayin is a string DNA binder. Wakayin also differed from camptothecin in that its cleavage complexes were much less stable than those of camptothecin in 0.5 M NaCl. Again in contrast to camptothecin, wakayin stabilized cleavage complexes poorly, if at all, at 0 degree C.
Kokoshka
J M
JM
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
Capson
T L
TL
Holden
J A
JA
Ireland
C M
CM
Barrows
L R
LR
D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D002166:Camptothecin / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000378:metabolism / Q000494:pharmacology*; D008387:Marine Toxins / Q000378:metabolism* / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D007364:Intercalating Agents; D008387:Marine Toxins; D059004:Topoisomerase I Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin