New [1,2,4]triazolo[4,3-c]quinazoline enhances cisplatin- and temozolomide-induced growth inhibition and apoptosis in HL-60 cells.
The purpose of this study was to investigate the therapeutic potential of a newly synthesized [1,2,4]triazolo[4,3-c]quinazoline (NTCHMTQ) alone and in combination with two anticancer drugs (cisplatin and temozolomide) against HL-60 leukemia cell line. The IC50 value of NTCHMTQ toward HL-60 cells was 19.7 microM. No apoptosis and cell cycle changes were observed in cells treated with 5 microM NTCHMTQ alone. Combination of non-toxic concentrations of NTCHMTQ (1-5 microM) with cisplatin or temozolomide sensitized HL-60 cells to these two drugs and significantly enhanced their efficacies, that is illustrated by combination indexes, sub-G0 cell fraction, apoptotic DNA fragmentation and caspase-3 activity. The results suggest that combined therapy of non-toxic concentrations of NTCHMTQ with chemotherapeutics may provide synergistic regimen for treatment of leukemia. However, further in vitro and in vivo experimental drug-cell and drug-drug studies are warranted.
Cipak
L
L
Cancer Research Institute, Slovak Academy of Science, Vlarska, Bratislava, Slovakia. exoncip@savba.sk
Letasiova
S
S
Repicky
A
A
Jantova
S
S
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D000077204:Temozolomide; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
C516744:3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl(1,2,4)triazolo(4,3-c)quinazoline; D000970:Antineoplastic Agents; D011799:Quinazolines; D014230:Triazoles; D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide