TY - JOUR
T1 - Induction of G2/M phase arrest and apoptosis of human leukemia cells by potent antitumor triazoloacridinone C-1305
AU - Augustin, Ewa
AU - Moś-Rompa, Anna
AU - Skwarska, Anna
AU - Witkowski, Jacek M.
AU - Konopa, Jerzy
PY - 2006/12/15
Y1 - 2006/12/15
N2 - In this study, we show that triazoloacridinone derivative C-1305, a potent antitumor compound, in human lymphoblastic (MOLT4) and promyelocytic (HL60) leukemia cells induces G2/M arrest followed by apoptosis. In both type of cells, C-1305 at biological relevant concentrations corresponding to EC90 value, induced a significant increase in the fraction of G2/M cells. The cell cycle perturbations were accompanied by the appearance of sub-G1 fraction, which can be considered as the apoptotic cells population. In both human leukemia cells apoptosis was additionally proved by appearance of DNA fragmentation, activation of caspase-3, PARP cleavage, externalization of phosphatydilserine as well as decrease of the mitochondrial transmembrane potential ΔΨm and ATP depletion. Treatment of lymphoblastic MOLT4 cells with the C-1305 at EC90 concentration, caused massive death by apoptosis. Compared to MOLT4 cells, the capacity of HL60 cells to execute apoptosis after C-1305 treatment at equitoxic dose was significantly weaker, but very effective at high concentration (4× EC90). These differences could originate from different sensitivity of both cell types to cytotoxic action of C-1305 (EC50 value for MOLT4 cells was 8 times lower than for HL60 cells and the EC90 value was 14 times lower, respectively). Collectively, these results show that C-1305 is a novel and potent compound which induces G2/M arrest and subsequent apoptosis of human leukemia cells. This strong ability to induce apoptosis of tumor cells support the view that C-1305 could be consider as a new potent and promising antitumor agent.
AB - In this study, we show that triazoloacridinone derivative C-1305, a potent antitumor compound, in human lymphoblastic (MOLT4) and promyelocytic (HL60) leukemia cells induces G2/M arrest followed by apoptosis. In both type of cells, C-1305 at biological relevant concentrations corresponding to EC90 value, induced a significant increase in the fraction of G2/M cells. The cell cycle perturbations were accompanied by the appearance of sub-G1 fraction, which can be considered as the apoptotic cells population. In both human leukemia cells apoptosis was additionally proved by appearance of DNA fragmentation, activation of caspase-3, PARP cleavage, externalization of phosphatydilserine as well as decrease of the mitochondrial transmembrane potential ΔΨm and ATP depletion. Treatment of lymphoblastic MOLT4 cells with the C-1305 at EC90 concentration, caused massive death by apoptosis. Compared to MOLT4 cells, the capacity of HL60 cells to execute apoptosis after C-1305 treatment at equitoxic dose was significantly weaker, but very effective at high concentration (4× EC90). These differences could originate from different sensitivity of both cell types to cytotoxic action of C-1305 (EC50 value for MOLT4 cells was 8 times lower than for HL60 cells and the EC90 value was 14 times lower, respectively). Collectively, these results show that C-1305 is a novel and potent compound which induces G2/M arrest and subsequent apoptosis of human leukemia cells. This strong ability to induce apoptosis of tumor cells support the view that C-1305 could be consider as a new potent and promising antitumor agent.
KW - Apoptosis
KW - C-1305
KW - Caspases
KW - G2/M arrest
KW - Mitochondria
KW - Triazoloacridinones
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UR - http://www.scopus.com/inward/citedby.url?scp=33751116980&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2006.07.035
DO - 10.1016/j.bcp.2006.07.035
M3 - Article
C2 - 16970926
AN - SCOPUS:33751116980
SN - 0006-2952
VL - 72
SP - 1668
EP - 1679
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 12
ER -