Topoisomerase inhibition by lucanthone, an adjuvant in radiation therapy.
OBJECTIVE
To determine whether lucanthone can inhibit human topoisomerases in vitro.


METHODS
Lucanthone was incubated with human topoisomerases II and I together with their plasmid substrates, to determine if lucanthone interfered with the catalytic activities of topoisomerases and if it enhanced the formation of DNA strand breaks, as determined by agarose gel electrophoresis of the resultant plasmid forms.


RESULTS
Incubation of the enzymes with lucanthone inhibited the catalytic activity of topoisomerases II and I. With topoisomerase II, it increased the abundance of DNA double strand breaks (cleavable complexes).


CONCLUSIONS
Lucanthone, like actinomycin D, inhibited topoisomerases II and I. It may act to enhance the yield of DNA double strand breaks in cells through a mechanism of topoisomerase II inhibition.
Bases
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Department of Radiation Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10467, USA.
Mendez
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D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004249:DNA Damage; D004278:DNA, Superhelical / Q000187:drug effects*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008154:Lucanthone / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004278:DNA, Superhelical; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D008154:Lucanthone