1993
DOI: 10.1007/bf00685675
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Decreased resistance toN,N-dimethylated anthracyclines in multidrug-resistant Friend erythroleukemia cells

Abstract: Doxorubicin-resistant Friend erythroleukemia cells, line F4-6 ADM2R, were selected by exposure of wild-type F4-6 cells to doxorubicin concentrations of up to 1 microgram/ml. In these cells, increased expression of multidrug resistance (MDR) genes was demonstrated by Northern blot analysis. The growth-inhibitory effect of doxorubicin, daunorubicin, N,N-dimethyldoxorubicin, N,N-dimethyldaunorubicin, morpholinodoxorubicin, and pyrromycin was comparatively investigated in resistant and wild-type cells. The doxorub… Show more

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Cited by 11 publications
(5 citation statements)
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“…OTS964, which is an N, N-dimethylated derivative of OTS514, caused tumor shrinkage even after discontinuation of treatment and resulted in complete tumor regression, which was not observed with OTS514. One possible mechanism for the improved in vivo efficacy of OTS964 may be that the dimethylation modification reduced the efflux of this compound from cancer cells and therefore increased its intracellular concentration, as reported previously for other compounds (28,29). Furthermore, oral administration of free OTS964 once every day for 2 weeks led to complete regression of tumors in all six mice.…”
Section: Discussionsupporting
confidence: 60%
“…OTS964, which is an N, N-dimethylated derivative of OTS514, caused tumor shrinkage even after discontinuation of treatment and resulted in complete tumor regression, which was not observed with OTS514. One possible mechanism for the improved in vivo efficacy of OTS964 may be that the dimethylation modification reduced the efflux of this compound from cancer cells and therefore increased its intracellular concentration, as reported previously for other compounds (28,29). Furthermore, oral administration of free OTS964 once every day for 2 weeks led to complete regression of tumors in all six mice.…”
Section: Discussionsupporting
confidence: 60%
“…Many chemical variations of anthracyclines have been synthesized before, including diMe-Doxo (64,65). However, these drugs were only tested for their ability to induce DNA damage, which was considered the main mechanism of therapeutic efficacy for anthracyclines (66).…”
Section: Discussionmentioning
confidence: 99%
“…One possible mechanism is that OTS964 is an N,N-dimethylated derivative of OTS514, and this dimethylation modification might reduce efflux of the compound in some cancer cells and therefore could increase its intracellular concentration, as exampled by other compounds (30,31).…”
Section: Discussionmentioning
confidence: 99%