Cytotoxicity and inhibitory properties against topoisomerase II of doxorubicin and its formamidine derivatives

• Autorzy: Kik K. , Studzian K. , Wasowska-Lukawska M. , Oszczapowicz I. , Szmigiero L.
• Języki publikacji: EN

Abstrakty

EN

 This work was undertaken to compare cytotoxicity, DNA damaging properties and effect on DNA cleavage by topoisomerase II of the anthracycline drug doxorubicin (DOX) and its two derivatives with a formamidino group containing a cyclic amine moiety such as morpholine (DOXM) or hexamethyleneimine (DOXH). The tetrazolium dye colorimetric assay was used to determine the cytotoxic activity of anthracyclines toward L1210 leukemia cells. DNA damage was measured by alkaline elution technique. The effect of anthracyclines on DNA cleavage was studied in a cell-free system containing supercoiled pBR322 DNA and purified human topoisomerase II. The cytotoxicity data and the results of studies on the mechanism of DNA break formation by anthracyclines at the cellular level and in the cell-free system showed that the presence of the formamidino group in the doxorubicin molecule reduced its ability to stimulate DNA cleavage by DNA topoisomerase II. Conclusion: DNA topoisomerase II is not a primary cellular target for DOXM or DOXH. An advantageous feature of formamidinoanthracyclines is their mechanism of cytotoxic action which is not related to the inhibition of DNA topoisomerase II. Therefore this class of anthracyclines seems to be a good source for selection of an anticancer drug directed toward cancer cells with the developed multidrug resistance attributed to the presence of altered DNA topoisomerase II.

Słowa kluczowe

EN

doxorubicin; topoisomerase II; inhibitory property; anthracycline; formamidino group; cytotoxicity

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2009
• Tom: 56
• Numer: 1
• Opis fizyczny: p.135-142,fig.,ref.

Twórcy

autor

Kik K.

• Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland

autor

Studzian K.

autor

Wasowska-Lukawska M.

autor

Oszczapowicz I.

autor

Szmigiero L.

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