Mitoxantrone affects topoisomerase activities in human breast cancer cells.
The effects of mitoxantrone, an antineoplastic DNA intercalator, on topoisomerase I and II were studied in two human breast cancer cell lines. A large increase of topoisomerase I activity was found when cells were exposed to various doses of mitoxantrone. Maximal effect was achieved with 20 and 40 ng/mL in T47D and MCF-7 cells respectively. The enhancement on topoisomerase I activity seemed to be reversible, to be dependent on time of exposure to the drug and to require cellular integrity. Type II topoisomerase was inhibited in T47D cells after treatment for one hour with 10 ng/mL of mitoxantrone and enzyme activity was undetectable at higher doses (40 ng/mL). This inhibitory effect did not take place in vitro unless the concentration of the intercalator was increased to 400-500 ng/mL.
D000880:Anthraquinones / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology*; D002460:Cell Line; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008942:Mitoxantrone; D011691:Puromycin / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
D000880:Anthraquinones; D059005:Topoisomerase II Inhibitors; D003609:Dactinomycin; D011691:Puromycin; D004317:Doxorubicin; D008942:Mitoxantrone; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II