A synthetic triptycene bisquinone, which blocks nucleoside transport and induces DNA fragmentation, retains its cytotoxic efficacy in daunorubicin-resistant HL-60 cell lines

In contrast to the parent triptycene (code name TTO), triptycene bisquinone (code name TT2) is cytostatic (IC50: 300 nM) and cytotoxic (IC50: 230 nM) in wild-type (WT), drug-sensitive HL-60 cells (HL-60-S) at day 4. Therefore , the effects of this new quinone antitumor drug were assessed and compared to those of daunorubicin (DAU, daunomycin) in the multidrug-resistant (MDR ) HL-60-RV and HL-60-R8 sublines, which respectively overexpress P-glycopro tein (P-gp) or multidrug resistance-associated protein (MRP). In contrast t o DAU, which loses its cytostatic [resistance factors (RFs): 22.9-35.7] and cytotoxic (RFs: 23.8-31.3) activities in MDR sublines, TT2 decreases tumor cell proliferation (R-Fs: 0.9-1.3) and viability (RFs: 0.9-1.5) as effecti vely in HL-60-S as in HL-60-RV and HL-60-R8 cells at days 2 and 4. Similarl y, DAU inhibits the rate of DNA synthesis less effectively in MDR than in p arental HL-60 cells (R-Fs: 8.1-11.9) but TT2 decreases the incorporation of (3)[H]-thymidine into DNA to the same degree in HL-60-S.