Restoration of doxorubicin responsiveness in doxorubicin-resistant P388 murine leukaemia cells by dipyrone.
The effect of dipyrone along with doxorubicin and mitoxantrone was studied alone and in combination on the 3H-thymidine (3H-TdR) incorporation in P388 leukaemia sensitive (P388/S) and resistant (P388/ADR) to doxorubicin. Dipyrone 10(-4) M demonstrated minimal inhibitory effect on DNA biosynthesis in both the sensitive and resistant cells. Doxorubicin and mitoxantrone at equimolar concentrations, indicated time and dose-dependent inhibition in 3H-TdR incorporation in the sensitive cells. The inhibition was more at the higher drug concentrations at 4 h drug exposure. Mitoxantrone showed cross-resistance in P388/ADR compared to P388/S. Both the drugs along with 10(-4) M dipyrone in the incubating medium revealed synergistic inhibitory activity in P388/S and P388/ADR. Observations indicate circumvention of doxorubicin and mitoxantrone resistance in P388/ADR by dipyrone.
D000632:Aminopyrine / Q000031:analogs & derivatives*; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004177:Dipyrone / Q000494:pharmacology*; D004317:Doxorubicin / Q000627:therapeutic use*; D004351:Drug Resistance; D004357:Drug Synergism; D007941:Leukemia P388 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D008942:Mitoxantrone / Q000627:therapeutic use; D013936:Thymidine / Q000378:metabolism; D014410:Tumor Stem Cell Assay
D000632:Aminopyrine; D004177:Dipyrone; D004317:Doxorubicin; D004247:DNA; D008942:Mitoxantrone; D013936:Thymidine